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CHE 102: LECTURE 8 From the Hydrogen Bond to the Blue
Planet to Jurassic Park
A 99-million-year old piece of amber discovered in 2016 by
Lida Xing in Myanmar (Burma). Suspended inside is the skull
of the smallest known bird, and, therefore, dinosaur, ever
discovered. The dinosaur’s skull is only a little more than half
an inch, from its beak to the end of its skull. The animal had
bulbous eyes that looked out from the sides of its head, rather
than straight ahead like the eyes of an owl or a human.
HYDROGEN BOND
A hydrogen bond (often abbreviated H-bond) is a type of
intermolecular bonding between a hydrogen atom and a “lone
pair” of electrons on an electron rich donor atom [particularly
the second-row elements N, O or F, and hydrogen].
Such an interacting system is generally denoted Dn–H···Ac
[Dn for donor, Ac for accepter] where the solid line signals a
polar covalent bond, and the dotted or dashed line indicates the
hydrogen bond. While hydrogen bonding has both covalent and
electrostatic (ionic) contributions, present evidence suggests
that the primary contribution is covalent.
Hydrogen bonds can be intermolecular (occurring between
separate molecules) or intramolecular or (occurring among parts
of the same molecule). Examples of both will be given below.
Depending on the nature of the donor and acceptor atoms which
constitute the bond, and the geometry and local environment,
the energy of a hydrogen bond can vary between 1 and 40
kcal/mol. This makes them somewhat stronger than nonpolar
(van der Waals) interactions, but weaker than fully covalent or
ionic bonds. Roughly speaking, the energy of a H-bond is about
5-10% the energy of a covalent bond. This type of bond can
occur in inorganic molecules such as water and in organic
molecules like proteins and DNA (see later discussion).
The hydrogen bond is responsible for many of the anomalous
physical and chemical properties of compounds of N, O, and F.
For example, intermolecular hydrogen bonding is responsible
for the high boiling point of water (100 °C) compared to
other hydrides that have much weaker hydrogen bonds.
Intramolecular hydrogen bonding plays an important role in the
structure of polymers, both synthetic and natural. It is also
partly responsible for the secondary and tertiary structures of
proteins and nucleic acids.
H-BONDS: WATER
Water is absolutely essential for our existence on Earth and
plays a pivotal role in physics, chemistry, biology and
geoscience. What makes water unique is not only its ubiquitous
presence on Earth but also the anomalous behavior of many of
its macroscopic properties.
The density, specific heat, viscosity and compressibility of
water behave in ways opposite to other liquids that we know. In
a glass of ice water, everything is, in a sense, upside down.
Strangely for the liquid state, water which freezes at 0 oC is the
densest at 4 ˚C, and therefore stays on the bottom. This is why
life can exist at the bottom of a lake and an ocean during
winter, even when the surface is frozen. At a more prosaic
level, this “inversion” in behavior is the reason why an ice cube
floats at the top of a glass of ice tea.
At the molecular level, the origin of this strange behavior,
unique to water among the important liquids, is still a subject of
great interest in physics and chemistry.
The crystal structure of solid water (ice) was shown in Lecture
4 . See also the graphic below. Notice that, accounting for both
covalent and H-bonds in water, a crystal of ice has a hexagonal
symmetry, which is why snowflakes have a hexagonal
symmetry.
A snowflake is a single ice crystal that has achieved a sufficient
size (either “by itself” or amalgamated with others) and falls
through the Earth’s atmosphere as snow. In supersaturated air
masses of water droplets in a cloud, each snowflake nucleates
around a dust particle, freezing and accreting in crystal form.
Complex shapes emerge as the flake moves through differing
temperature and humidity zones in the atmosphere, so that
individual snowflakes differ in detail from one another. They
are categorized in eight broad classifications and at least 80
individual variants. The main constituent shapes for ice
crystals, from which combinations may occur, are needle,
column, plate, and rime. Snow appears white in color despite
being made of clear ice. This is due to diffuse reflection of the
whole spectrum of light by the small crystal facets of
snowflakes.
THE BLUE PLANETThe origin of water on Earth is the subject
of an extensive body of research in the fields of planetary
science, astronomy and astrobiology. Earth is unique among
the rocky planets in the Solar System in that it is the only planet
known to have oceans of liquid water on its surface. Liquid
water, which is necessary for life, continues to exist on the
surface of Earth because the planet is at a distance far enough
from the Sun that it does not lose its water to the greenhouse
effect, but not so far that low temperatures cause all water on
the planet to freeze.
Earth could not have condensed from the protoplanetary disk
with its current oceans of water because the early inner Solar
System was far too hot for water to condense. Instead, water
and other volatiles must have been delivered to Earth from the
Solar System later in its history. Modern geochemical evidence
suggests that water was delivered to Earth by impacts from
icy planetesimals similar in composition to modern asteroids in
the outer edges of the asteroid belt.
WATER: Essential for Life on Earth Living System
Water is fundamental to the survival of organisms. Doctors
recommend drinking 8 cups of water a day in order to maintain
a healthy lifestyle. Clean water is one of the primary concerns
of all countries, especially Third World countries. Wars have
been fought over who gets the rights to drink from the source of
water. Recall the movie, “Lawrence of Arabia.” Wars in the
future will likely not be fought over oil or mineral resources,
but water.
Why is this substance so vital to the survival of all life?
First, liquid water is essential for biochemical reactions by
providing a medium which facilitates the transport of vital
nutrients from one place to another within a cell.
Second, water, as a polar molecule, is considered the “universal
solvent”, in that everything dissolves in water to some degree,
allowing nutrients to be integrated into water with relative ease.
NOTE:
The solvent properties of water or other substances is summed
up in the simple phrase
“Like dissolves like.”
Table salt, which is composed of Na+ and Cl- ions, dissolves
readily in water, a polar molecule.
Salad dressing, oil and vinegar, left standing, will separate into
a vinegar (polar) phase and an oil (nonpolar) phase. You have
to shake the bottle to mix the two (which then forms an
emulsion).
Additives aside, gasoline is composed of the nonpolar
hydrocarbon molecule octane (C8H18).
Octane
When filling up your gas tank, if you happen to spill gas on a
wet pavement you may have noticed technicolor fringes. These
result because gasoline and water don’t mix. Water has
a higher density than octane (0.993 g/cm3 vs 0.706 g/cm3), so
the gas floats on top. This thin film of oil, refracted by sunlight,
produces the “rainbow” fringes.
In understanding the d=3 dimensional structure of proteins (See
Lecture 6), amino acids with polar side chains “stick out” into
the aqueous medium of a cell, whereas amino acids with
nonpolar side chains are buried away inside the structure. This
sequestering of nonpolar amino acids in the interior of a protein
was analyzed in 1953 by my PhD advisor at Princeton, Walter
Kauzmann, who baptized the effect “hydrophobic bonding.”
Today, the hydrophobic effect is discussed extensively in
standard textbooks on biochemistry and cell biology.
Third, water also helps enzymes to function [Recall, enzymes
are proteins that catalyze chemical reactions, thus speeding up
the reaction. See Lecture 6].
Another unique thing about water is that all three states (liquid,
solid and gas) exists naturally in nature. [Remember Thales?
See Lecture 1] This allows the water cycle to occur in nature,
which replenishes water around the world.
Pure water has a wide range of temperature between its freezing
and boiling points (100 oC). Both temperatures can be
manipulated with salt and other minerals.
Water has a very high specific heat, which means it takes a lot
of energy to heat it up. This allows water to survive the intense
heat variations that Earth has without evaporating at once, and
helps to moderate the temperature of the planet thanks to the
oceans.
As noted above, a remarkable characteristic of water is that
when it turns into solid ice, it expands instead of contracts,
unlike a normal solid. The result is that ice floats above liquid
water, thus preventing it from displacing water and causing the
ocean levels to rise, and also allowing Arctic and Antarctic life
to thrive.
H-BONDS: The α-Helix in Proteins and the Double Helix in
Nucleic Acids
The alpha helix (α-helix) in the secondary structure of proteins
is a right-hand helix in which every N-H group in one amino
acid (residue) H-bonds to the C=O group of an amino
acid located three or four residues earlier along the sequence of
amino acids making up the protein.
The alpha helix is called a Pauling–Corey–Branson α-helix. The
name 3.613 helix is also used for this type of helix, specifying
the average number of amino acids (residues) per helical turn,
with 13 atoms being involved in the ring formed by the
hydrogen bond. See below.
H-bonds break when a protein is subject to increased
temperature. This is what happens when you fry an egg for
breakfast. The egg white will quickly turn from clear and runny
to white and firm. Heat energy agitates the egg-white proteins,
making them bounce around and hit water molecules and other
proteins. These collisions break the weak
H-bonds that held the protein curled up in its “native state”,
allowing the chain of amino acids to partly unfold – a process
called denaturation.
When these agitated proteins bump against one another, new
and stronger chemical bonds form between them. As these
proteins join together in an interconnected web, the egg white
congeals into a solid, and you have a “sunny side up egg.”
Hydrogen bonds are also responsible for specific base-pair
formation in the DNA double helix (See Lecture 6) and a
major contributor to the stability of the DNA double
helix structure. A hydrogen-bond donor includes
the hydrogen atom and the atom with which it is most tightly
linked .
In genetics, DNA replication is the process by
which DNA makes a copy of itself during cell division. The
first step in DNA replication is to 'unzip' the double helix
structure of the DNA molecule. H-bonds between base pairs
(See Lecture 6) are broken and the two separated strands then
act as templates for making new strands of DNA.
EVOLUTION of LIFE on EARTH: AGE of the DINOSAURS
Dinosaurs are a diverse group of reptiles. They first appeared
during the Triassic period, between 243 and 233.23 million
years ago. They became the dominant terrestrial vertibrates
after the Triassic-Jurassic extinction event 201.3 million years
ago. Their dominance continued through the Jurassic and
Cretaceous periods.
The fossil record demonstrates that birds are modern feathered
dinosaurs (See top of Lecture), having evolved during the Late
Jurassic epoch. Indeed, birds were the only dinosaur lineage to
survive the Cretaceous-Palogene extinction event approximately
66 million years ago.
The Chicxulub crater is an impact crater buried underneath
the Yucatán Peninsula in Mexico.
It was formed when a large asteroid or comet about 6.8 to 50.3
miles in diameter, struck the Earth. The date of the impact
coincides precisely with the Cretaceous-Paleogene boundary
(commonly known as the "K–Pg boundary" ), slightly less than
66 million years ago, and a widely accepted theory is that
worldwide climate disruption from the event was the cause of
the a mass extinction in which 75% of plant and animal species
on Earth became extinct. Dinosaurs can be divided into avian
dinosaurs, or birds; and non-avian dinosaurs, which are all
dinosaurs other than birds. The non-avian dinosaurs didn’t
survive.
AMBER
Amber, fossilized tree resin, has long been appreciated for its
color and natural beauty. Much valued from antiquity to the
present as a gemstone, amber has also been made into a variety
of decorative objects. Below is the Amber Room in the
Catherine Palace in Saint Petersburg, the Russian port on the
Baltic Sea, founded by the Czar Peter the Great in 1703.
A town (Amer or Amber) in Rajasthan, India, founded around
1036, is famous for its Amber Fort.
Ganesh Pol Entrance
My work with the World Bank and the International Institute of
Theoretical and Applied Physics took me to many parts of the
World. I’ve seen both of the above, and they are stunning.
Insects trapped in tree resin, became “fossilized.”
The science underlying Jurassic Park is that the DNA isolated
from a dinosaur trapped in tree resin, and then fossilized, can
be extracted using standard techniques in biochemistry and used
to create “the original.”
Lastly, from at least the 16th century BC, amber was
transported from Northern Europe to the Mediterranean region.
Recalling Lecture 1, the breast ornament of the Egyptian
pharaoh Tutankhamen (c. 1333–1324 BC) contains large amber
beads from the Baltic Sea area (today’s Poland). Amber was
sent from the North Sea to the temple of Apollo at Delphi as an
offering. Ancient trade routes in Asia (the Silk Road) brought
amber from the Black Sea to China, where it was customary to
burn amber during large festivities.
Below is an expensive decorative object made of rare white
amber, an artist’s representation of the Great Wall of China
(also a “must see”).
LECTURE 99From Neurons to the Nervous System to the Brain
The neuron's place as the primary functional unit of the nervous
system was first recognized in the late 19th century by the
Spanish anatomist Santiago Ramón y Cajal (1852-1934), a
neuroscientist and pathologist specializing in neuroanatomy
and, especially, the central nervous system.
In 1888 Ramón y Cajal published a paper about the pigeon
cerebellum. In this paper, he stated that he could not find
evidence for cross connections (anastomosis) between axons
and dendrites and called each nervous element "an absolutely
autonomous canton." This became known as the neuron
doctrine, one of the central tenets of modern neurobiology.
Above is his 1899 drawing of neurons in the pigeon cerebellum.
This Lecture focuses on the chemistry of neurons, specialized
cells that transmit chemical and electrical signals to facilitate
communication between the brain and the body. In learning
about a new field, one can get befuddled very quickly with the
jargon used by experts in the field and get lost, not being able
“to see the forest for the trees.” So, before each section, I give
a summary of Key Points and Key Terms you will need to
understand that section. At the expense of “over kill,” I have
repeated earlier “points” and “terms” at subsequent points in the
Lecture so that you won’t have to “backtrack” to figure out
what is going on.
Neurons are specialized cells that transmit chemical and
electrical signals in the brain. They are the basic building
blocks of the central nervous system.
Key Points:
· Neurons are specialized cells that transmit chemical and
electrical signals in the brain; they are the basic building blocks
of the central nervous system.
· The primary components of the neuron are the soma (cell
body), the axon (a long slender projection that conducts
electrical impulses away from the cell body), dendrites (tree-
like structures that receive messages from other neurons), and
synapses (specialized junctions between neurons).
· Some axons are covered with myelin, a fatty material that acts
as an insulator and conductor to speed up the process of
communication.
· Sensory neurons are neurons responsible for converting
external stimuli from the environment into corresponding
internal stimuli.
· Motor neurons are neurons located in the central nervous
system (CNS); they project their axons outside of the CNS to
directly or indirectly control muscles.
· Interneurons act as the “middle men” between sensory and
motor neurons, which convert external stimuli to internal
stimuli and control muscle movement, respectively.
Key Terms:
· glial cell: Non-neuronal cells that provide structure and
support to neurons.
· synapse: The junction between the terminal of a neuron and
either another neuron or a muscle or gland cell, over which
nerve impulses pass.
· myelin: A white, fatty material composed of lipids and
lipoproteins that surrounds the axons of nerves and facilitates
swift communication.
· nodes of Ranvier: Periodic gaps in the myelin sheath where
the signal is recharged as it moves along the axon.
The neuron is the basic building block of the brain and central
nervous system. The brain is made up entirely of neurons and
glial cells. Nearly 86 billion neurons work together within the
nervous system to communicate with the rest of the body.
Fun facts: The Milky Way galaxy has an estimated 100 billion
stars. It is estimated that there are 10 trillion galaxies in the
observable universe. Multiplying that by the Milky Way's
estimated 100 billion stars results in a large number indeed:
1,000,000,000,000,000,000,000,000
stars.
Given this astronomically-large value, the probability that there
is (at least) one star with a planet “just the right distance” from
that star is quite high. Whether there are large bodies of H2O
on this planet is another matter but, if so, assuming the same
distribution of elements as on planet Earth, the chemistry of
Carbon can kick in and life on that planet is possible.
Neurons are responsible for consciousness and thought to pain
and hunger. You need almost as many neurons to function as
there are stars in our Milky Way.
Structures of a Neuron
In addition to having all the normal components of a cell
(nucleus, organelles, etc.), neurons also contain unique
structures for receiving and sending the electrical signals that
make neuronal communication possible.
The structure of a neuron: The above image shows the basic
structural components of an average neuron, including the
dendrite, cell body, nucleus, Node of Ranvier, myelin sheath,
Schwann cell, and axon terminal.
Dendrite
Dendrites are branch-like structures extending away from the
cell body, and their job is to receive messages from other
neurons and allow those messages to travel to the cell body.
Although some neurons do not have any dendrites, other types
of neurons have multiple dendrites. Dendrites can have small
protrusions called dendritic spines, which further increase
surface area for possible connections with other neurons.
Cell Body
Like other cells, each neuron has a cell body (or soma) that
contains a nucleus, smooth and rough endoplasmic reticulum,
Golgi apparatus, mitochondria, and other cellular components.
Axon
An axon is a tube-like structure that carries an electrical
impulse from the cell body (or from another cell’s dendrites) to
the structures at opposite end of the neuron—axon terminals,
which can then pass the impulse to another neuron. The cell
body contains a specialized structure, the axon hillock, which
serves as a junction between the cell body and the axon.
Synapse
The synapse is the chemical junction between the axon
terminals of one neuron and the dendrites of the next. It is a gap
where specialized chemical interactions can occur, rather than
an actual structure.
Function of a Neuron
The specialized structure and organization of neurons allows
them to transmit signals in the form of electric impulses from
the brain to the body and back. Individually, neurons can pass a
signal all the way from their own dendrites to their own axon
terminals. At a higher level, neurons are organized in long
chains, allowing them to pass signals very quickly from one to
the other. One neuron’s axon will connect chemically to another
neuron’s dendrite at the synapse between them. Electrically
charged chemicals flow from the first neuron’s axon to the
second neuron’s dendrite, and that signal will then flow from
the second neuron’s dendrite, down its axon, across a synapse,
into a third neuron’s dendrites, and so on.
This is the basic chain of neural signal transmission, which is
how the brain sends signals to the muscles to make them move,
and how sensory organs send signals to the brain. It is important
that these signals can happen quickly, and they do.
Think of how fast you drop a hot potato—before you even
realize it is hot. This is because the sense organ (in this case,
the skin) sends the signal “This is hot!” to neurons with very
long axons that travel up the spine to the brain. If this didn’t
happen quickly, people would burn themselves.
Other Structures
Dendrites, cell bodies, axons, and synapses are the basic parts
of a neuron, but other important structures and materials
surround neurons to make them more efficient.
Myelin Sheath
Some axons are covered with myelin, a fatty material that wraps
around the axon to form the myelin sheath. This external
coating functions as insulation to minimize dissipation of the
electrical signal as it travels down the axon. Myelin’s presence
on the axon greatly increases the speed of conduction of the
electrical signal, because the fat prevents any electricity from
“leaking out”. This insulation is important, as the axon from a
human motor neuron can be as long as a meter—from the base
of the spine to the toes. Periodic gaps in the myelin sheath are
called nodes of Ranvier. At these nodes, the signal is
“recharged” as it travels along the axon.
Glial Cells
The myelin sheath is not actually part of the neuron. Myelin is
produced by glial cells (or simply glia, or “glue” in Greek),
which are non-neuronal cells that provide support for the
nervous system. Glia function to hold neurons in place (hence
their Greek name), supply them with nutrients, provide
insulation, and remove pathogens and dead neurons. In the
central nervous system, the glial cells that form the myelin
sheath are called oligodendrocytes; in the peripheral nervous
system, they are called Schwann cells.
Neuron in the central nervous system: This neuron diagram also
shows the oligodendrocyte, myelin sheath, and nodes of
Ranvier.
Types of Neurons
There are three major types of neurons: sensory neurons, motor
neurons, and interneurons. All three have different functions,
but the brain needs all of them to communicate effectively with
the rest of the body (and vice versa).
Sensory Neurons
Sensory neurons are neurons responsible for converting external
stimuli from the environment into corresponding internal
stimuli. They are activated by sensory input, and send
projections to other elements of the nervous system, ultimately
conveying sensory information to the brain or spinal cord.
Unlike the motor neurons of the central nervous system (CNS),
whose inputs come from other neurons, sensory neurons are
activated by physical stimuli (such as visible light, sound, heat,
physical contact, etc.) or by chemical signals (such as smell and
taste).
Most sensory neurons are pseudounipolar, meaning they have an
axon that branches into two extensions—one connected to
dendrites that receive sensory information and another that
transmits this information to the spinal cord.
Motor Neurons
Motor neurons are neurons located in the central nervous
system, and they project their axons outside of the CNS to
directly or indirectly control muscles. The interface between a
motor neuron and muscle fiber is a specialized synapse called
the neuromuscular junction. The structure of motor neurons
is multipolar, meaning each cell contains a single axon and
multiple dendrites. This is the most common type of neuron.
Interneurons
Interneurons are neither sensory nor motor; rather, they act as
the “middle men” that form connections between the other two
types. Located in the CNS, they operate locally, meaning their
axons connect only with nearby sensory or motor neurons.
Interneurons can save time and therefore prevent injury by
sending messages to the spinal cord and back instead of all the
way to the brain. Like motor neurons, they are multipolar in
structure.
Stages of the Action Potential
Neural impulses occur when a stimulus depolarizes a cell
membrane, prompting an action potential which sends an “all or
nothing” signal.
Key Points:
· The neurons (or excitable nerve cells) of the nervous system
conduct electrical impulses, or signals, that serve as
communication between sensory receptors, muscles and glands,
and the brain and spinal cord.
· An action potential occurs when an electrical signal disrupts
the original balance of Na+ and K+ within a cell membrane,
briefly depolarizing the concentrations of each.
· An electrical impulse travels along the axon via depolarized
voltage-gated ion channels in the membrane, and can either
“jump” along a myelinated area or travel continuously along an
unmyelinated area.
· While an action potential is being generated by a cell, no other
action potential may be generated until the cell’s channels
return to their resting state.
· Action potentials generated by neural impulses are “all or
nothing,” meaning the signal reaches the threshold for
communication or it doesn’t. No signal is stronger or weaker
than another.
Key Terms:
· polarity: The spatial differences in the shape, structure, and
function of cells. Almost all cell types exhibit some sort of
polarity, which enables them to carry out specialized functions.
· action potential: A short-term change in the electrical
potential that travels along a cell, such as a nerve or muscle
fiber, and allows nerves to communicate.
· neural impulse: The signal transmitted along a nerve fiber,
either in response to a stimulus (such as touch, pain, or heat), or
as an instruction from the brain (such as causing a muscle to
contract).
· resting potential: The nearly latent membrane potential of
inactive cells.
Neural Impulses in the Nervous System
The central nervous system (CNS) goes through a three-step
process when it functions: sensory input, neural processing, and
motor output. The sensory input stage is when the neurons (or
excitable nerve cells) of the sensory organs are excited
electrically. Neural impulses from sensory receptors are sent to
the brain and spinal cord for processing. After the brain has
processed the information, neural impulses are then conducted
from the brain and spinal cord to muscles and glands, which is
the resulting motor output.
A neuron affects other neurons by releasing a neurotransmitter
that binds to chemical receptors. The effect upon the
postsynaptic (receiving) neuron is determined not by the
presynaptic (sending) neuron or by the neurotransmitter itself,
but by the type of receptor that is activated.
A neurotransmitter can be thought of as a key, and a receptor as
a lock: the key unlocks a certain response in the postsynaptic
neuron, communicating a particular signal. However, in order
for a presynaptic neuron to release a neurotransmitter to the
next neuron in the chain, it must go through a series of changes
in electric potential.
Stages of Neural Impulses
“Resting potential ” is the name for the electrical state when a
neuron is not actively being signaled. A neuron at resting
potential has a membrane with established amounts of sodium
(Na+) and potassium (K+) ions on either side, leaving the inside
of the neuron negatively charged relative to the outside.
The action potential is a rapid change in polarity that moves
along the nerve fiber from neuron to neuron. In order for a
neuron to move from resting potential to action potential—a
short-term electrical change that allows an electrical signal to
be passed from one neuron to another—the neuron must be
stimulated by pressure, electricity, chemicals, or another form
of stimuli. The level of stimulation that a neuron must receive
to reach action potential is known as the threshold of excitation,
and until it reaches that threshold, nothing will happen.
Different neurons are sensitive to different stimuli, although
most can register pain.
The action potential has several stages.
1. Depolarization: A stimulus starts the depolarization of the
membrane. Depolarization is caused when positively charged
sodium ions rush into a nerve cell. As these positive ions rush
in, the membrane of the stimulated cell reverses its polarity so
that the outside of the membrane is negative relative to the
inside.
2. Repolarization. Once the electric gradient has reached the
threshold of excitement, the “downswing” of repolarization
begins. The channels that let the positive sodium ion channels
through close up, while channels that allow positive potassium
ions open, resulting in the release of positively charged
potassium ions from the neuron. This expulsion acts to restore
the localized negative membrane potential of the cell, bringing
it back to its normal voltage.
3. Refractory Phase. The refractory phase takes place over a
short period of time after the depolarization stage. Shortly after
the sodium gates open, they close and go into an inactive
conformation. The sodium gates cannot be opened again until
the membrane is repolarized to its normal resting potential. A
sodium-potassium pump returns sodium ions to the outside and
potassium ions to the inside. During the refractory phase this
particular area of the nerve cell membrane cannot be
depolarized. Therefore, the neuron cannot reach action potential
during this “rest period.”
Action potentials: A neuron must reach a certain threshold in
order to begin the depolarization step of reaching the action
potential.
This process of depolarization, repolarization, and recovery
moves along a nerve fiber from neuron to neuron like a very
fast wave. While an action potential is in progress, another
cannot be generated under the same conditions. In unmyelinated
axons (axons that are not covered by a myelin sheath), this
happens in a continuous fashion because there are voltage-gated
channels throughout the membrane. In myelinated axons (axons
covered by a myelin sheath), this process is described as
saltatory because voltage-gated channels are only found at the
nodes of Ranvier, and the electrical events seem to “jump” from
one node to the next.
Saltatory conduction is faster than continuous conduction. The
diameter of the axon also makes a difference, as ions diffusing
within the cell have less resistance in a wider space. Damage to
the myelin sheath from disease can cause severe impairment of
nerve-cell function. In addition, some poisons and drugs
interfere with nerve impulses by blocking sodium channels in
nerves. More on this point in the next Lecture.
All-or-none Signals
The amplitude of an action potential is independent of the
amount of current that produced it. In other words, larger
currents do not create larger action potentials. Therefore, action
potentials are said to be all-or-none signals, since either they
occur fully or they do not occur at all. The frequency of action
potentials is correlated with the intensity of a stimulus. This is
in contrast to receptor potentials, whose amplitudes are
dependent on the intensity of a stimulus.
Reuptake
Reuptake refers to the reabsorption of a neurotransmitter by a
presynaptic (sending) neuron after it has performed its function
of transmitting a neural impulse. Reuptake is necessary for
normal synaptic physiology because it allows for the recycling
of neurotransmitters and regulates the neurotransmitter level in
the synapse, thereby controlling how long a signal resulting
from neurotransmitter release lasts.
Mechanics of the Action Potential
The synapse is the site at which a chemical or electrical
exchange occurs between the presynaptic and postsynaptic cells.
Key Points:
· Receptors are pores that admit chemical or electrical signals
into the postsynaptic cell. There are two main types of receptor:
ligand-gated ion channels, which receive neurostransmitters,
and g-protein coupled receptors, which do not.
· There are two types of possible reactions at the synapse: a
chemical reaction or an electrical reaction.
· During a chemical reaction, neurotransmitters trigger the
opening of ligand-gated ion channels on the membrane of the
postsynaptic cell, resulting in a modification of the cell’s
interior chemical composition and, in some cases, physical
structure.
· In an electrical reaction, the electrical charge of one cell is
influenced by another.
· Although electrical synapses yield faster reactions, chemical
synapses result in stronger, more complex changes to the
postsynaptic cell.
Key Terms:
· vesicle: A membrane-bound compartment found in a cell.
· action potential: A short-term change in the electrical
potential that travels along a cell, such as a nerve or muscle
fiber, and allows nerves to communicate.
· depolarization: The act of depriving of polarity, or the result
of such action; reduction to an unpolarized condition.
· membrane potential: The voltage across the cell membrane,
with the inside relative to the outside.
Synapses
The synapse is the junction where neurons trade information. It
is not a physical component of a cell but rather a name for the
gap between two cells: the presynaptic cell (giving the signal)
and the postsynaptic cell (receiving the signal). There are two
types of possible reactions at the synapse—chemical or
electrical. During a chemical reaction, a chemical called a
neurotransmitter is released from one cell into another. In an
electrical reaction, the electrical charge of one cell is influenced
by the charge an adjacent cell.
The electrical response of a neuron to multiple synaptic inputs:
Synaptic responses summate in order to bring the postsynaptic
neuron to the threshold of excitation, so it can fire an action
potential (represented by the peak on the chart).
All synapses have a few characteristics in common:
· Presynaptic cell: a specialized area within the axon of the
giving cell that transmits information to the dendrite of the
receiving cell.
· Synaptic cleft: the small space at the synapse that receives
neurotransmitters.
· G-protein coupled receptors: receptors that sense molecules
outside the cell and thereby activate signals within it.
· Ligand-gated ion channels: receptors that are opened or closed
in response to the binding of a chemical messenger.
· Postsynaptic cell: a specialized area within the dendrite of the
receiving cell that contains receptors designed to process
neurotransmitters.
The Electrical Synapse
The stages of an electrical reaction at a synapse are as follows:
1. Resting potential. The membrane of a neuron is normally at
rest with established concentrations of sodium ions (Na+) and
potassium ions (K+) on either side. The membrane potential (or,
voltage across the membrane) at this state is -70 mV, with the
inside being negative relative to the outside.
2. Depolarization. A stimulus begins the depolarization of the
membrane. Depolarization, also referred to as the “upswing,”
occurs when positively charged sodium ions (Na+) suddenly
rush through open sodium gates into a nerve cell. If the
membrane potential reaches -55 mV, it has reached the
threshold of excitation. Additional sodium rushes in, and the
membrane of the stimulated cell actually reverses its polarity so
that the outside of the membrane is negative relative to the
inside. The change in voltage stimulates the opening of
additional sodium channels (called a voltage-gated ion channel),
providing what is known as a positive feedbackloop. Eventually,
the cell potential reaches +40 mV, or the action potential.
3. Repolarization. The “downswing” of repolarization is caused
by the closing of sodium ion channels and the opening of
potassium ion channels, resulting in the release of positively
charged potassium ions (K+) from the nerve cell. This expulsion
acts to restore the localized negative membrane potential of the
cell.
4. Refractory Phase. The refractory phase is a short period of
time after the repolarization stage. Shortly after the sodium
gates open, they close and go into an inactive conformation
where the cell’s membrane potential is actually even lower than
its baseline -70 mV. The sodium gates cannot be opened again
until the membrane has completely repolarized to its normal
resting potential, -70 mV. The sodium-potassium pump returns
sodium ions to the outside and potassium ions to the inside.
During the refractory phase this particular area of the nerve cell
membrane cannot be depolarized; the cell cannot be excited.
The Chemical Synapse
The process of a chemical reaction at the synapse has some
important differences from an electrical reaction. Chemical
synapses are much more complex than electrical synapses,
which makes them slower, but also allows them to generate
different results. Like electrical reactions, chemical reactions
involve electrical modifications at the postsynaptic membrane,
but chemical reactions also require chemical messengers, such
as neurotransmitters, to operate.
Neuron & chemical synapse: This image shows electric
impulses traveling between neurons; the inset shows a chemical
reaction occurring at the synapse.
A basic chemical reaction at the synapse undergoes a few
additional steps:
1. The action potential (which occurs as described above)
travels along the membrane of the presynaptic cell until it
reaches the synapse. The electrical depolarization of the
membrane at the synapse causes channels to open that are
selectively permeable, meaning they specifically only allow the
entry of positive sodium ions (Na+).
2. The ions flow through the presynaptic membrane, rapidly
increasing their concentration in the interior.
3. The high concentration activates a set of ion-sensitive
proteins attached to vesicles, which are small membrane
compartments that contain a neurotransmitter chemical.
4. These proteins change shape, causing the membranes of some
“docked” vesicles to fuse with the membrane of the presynaptic
cell. This opens the vesicles, which releases their
neurotransmitter contents into the synaptic cleft, the narrow
space between the membranes of the pre- and postsynaptic cells.
5. The neurotransmitter diffuses within the cleft. Some of it
escapes, but the rest of it binds to chemical receptor molecules
located on the membrane of the postsynaptic cell.
6. The binding of neurotransmitter causes the receptor molecule
to be activated in some way. Several types of activation are
possible, depending on what kind of neurotransmitter was
released. In any case, this is the key step by which the synaptic
process affects the behavior of the postsynaptic cell.
7. Due to thermal shaking, neurotransmitter molecules
eventually break loose from the receptors and drift away.
8. The neurotransmitter is either reabsorbed by the presynaptic
cell and repackaged for future release, or else it is broken down
metabolically.
Differences Between Electrical and Chemical Synapses
· Electrical synapses are faster than chemical synapses because
the receptors do not need to recognize chemical messengers.
The synaptic delay for a chemical synapse is typically about 2
milliseconds, while the synaptic delay for an electrical synapse
may be about 0.2 milliseconds.
· Because electrical synapses do not involve neurotransmitters,
electrical neurotransmission is less modifiable than chemical
neurotransmission.
· The response is always the same sign as the source. For
example, depolarization of the presynaptic membrane will
always induce a depolarization in the postsynaptic membrane,
and vice versa for hyperpolarization.
· The response in the postsynaptic neuron is generally smaller
in amplitude than the source. The amount of attenuation of the
signal is due to the membrane resistance of the presynaptic and
postsynaptic neurons.
· Long-term changes can be seen in electrical synapses. For
example, changes in electrical synapses in the retina of your
eyeare seen during light and dark adaptations of the retina.
Neurotransmitters
Neurotransmitters are chemicals that transmit signals from a
neuron across a synapse to a target cell.
Key Points:
· Neurotransmitters dictate communication between cells by
binding to specific receptors and depolarizing or
hyperpolarizing the cell.
· Inhibitory neurotransmitters cause hyperpolarization of the
postsynaptic cell; excitatory neurotransmitters cause
depolarization of the postsynaptic cell.
· Too little of a neurotransmitter may cause the over
accumulation of proteins, leading to disorders like Alzheimer’s
disease. Too much of a neurotransmitter may block receptors
required for proper brain function, leading to disorders like
schizophrenia.
· The three neurotransmitter systems in the brain are
cholinergic, amino acids, and biogenic amines.
Key Terms
· reuptake: The reabsorption of a neurotransmitter by a neuron
after the transmission of a neural impulse across a synapse.
· vesicle: A membrane-bound compartment found in a cell.
· action potential: A short-term change in the electrical
potential that travels along a cell (such as a nerve or muscle
fiber); the basis of neural communication.
Neurotransmitters are chemicals that transmit signals from a
neuron to a target cell across a synapse. When called upon to
deliver messages, they are released from their synaptic vesicles
on the presynaptic (giving) side of the synapse, diffuse across
the synaptic cleft, and bind to receptors in the membrane on the
postsynaptic (receiving) side.
An action potential is necessary for neurotransmitters to be
released, which means that neurons must reach a certain
threshold of electric stimulation in order to complete the
reaction. A neuron has a negative charge inside the cell
membrane relative to the outside of the cell membrane; when
stimulation occurs and the neuron reaches the threshold of
excitement this polarity is reversed. This allows the signal to
pass through the neuron. When the chemical message reaches
the axon terminal, channels in the postsynaptic cell membrane
open up to receive neurotransmitters from vesicles in the
presynaptic cell.
Inhibitory neurotransmitters cause hyperpolarization of the
postsynaptic cell (that is, decreasing the voltage gradient of the
cell, thus bringing it further away from an action potential),
while excitatory neurotransmitters cause depolarization
(bringing it closer to an action potential).
Neurotransmitters match up with receptors like a key in a lock.
A neurotransmitter binds to its receptor and will not bind to
receptors for other neurotransmitters, making the binding a
specific chemical event.
There are several systems of neurotransmitters found at various
synapses in the nervous system. The following groups refer to
the specific chemicals, and within the groups are specific
systems, some of which block other chemicals from entering the
cell and some of which permit the entrance of chemicals that
were blocked before.
Cholinergic System
The cholinergic system is a neurotransmitter system of its own,
and is based on the neurotransmitter acetylcholine (ACh). This
system is found in the autonomic nervous system, as well as
distributed throughout the brain.
The cholinergic system has two types of receptors: the nicotinic
receptor and the acetylcholine receptor, which is known as the
muscarinic receptor. Both of these receptors are named for
chemicals that interact with the receptor in addition to the
neurotransmitter acetylcholine.
Nicotine, the chemical in tobacco, binds to the nicotinic
receptor and activates it similarly to acetylcholine. Muscarine, a
chemical product of certain mushrooms, binds to the muscarinic
receptor. However, they can not bind to each others’ receptors.
Amino Acids
Another group of neurotransmitters are amino acids, including
glutamate (Glu), GABA (gamma-aminobutyric acid, a derivative
of glutamate), and glycine (Gly). These amino acids have an
amino group and a carboxyl group in their chemical structures.
Glutamate is one of the 20 amino acids used to make proteins.
See Lecture 6.
Each amino acid neurotransmitter is its own system, namely the
glutamatergic, GABAergic, and glycinergic systems. They each
have their own receptors and do not interact with each other.
Amino acid neurotransmitters are eliminated from the synapse
by reuptake. A pump in the cell membrane of the presynaptic
element, or sometimes a neighboring glial cell, clears the amino
acid from the synaptic cleft so that it can be recycled,
repackaged in vesicles, and released again.
The reuptake process: This illustration shows the process of
reuptake, in which leftover neurotransmitters are returned to
vesicles in the presynaptic cell.
Biogenic Amines
Another class of neurotransmitter is the biogenic amine, a group
of neurotransmitters made enzymatically from amino acids.
They have amino groups in them, but do not have carboxyl
groups and are therefore no longer classified as amino acids.
Neuropeptides
A neuropeptide is a neurotransmitter molecule made up of
chains of amino acids connected by peptide bonds, similar to
proteins. However, proteins are long molecules while some
neuropeptides are quite short. Neuropeptides are often released
at synapses in combination with another neurotransmitter.
Dopamine
Dopamine is the best-known neurotransmitter of the
catecholamine group. The brain includes several distinct
dopamine systems, one of which plays a major role in reward-
motivated behavior. Most types of reward increase the level of
dopamine in the brain, and a variety of addictive drugs increase
dopamine neuronal activity. Other brain dopamine systems are
involved in motor control and in controlling the release of
several other important hormones ( a regulatory substance
produced in an organismand transported in tissue fluids such as
blood or sap to stimulate specific cells or tissues into action ).
More on this in the next Lecture.
Effect on the Synapse
The effect of a neurotransmitter on the postsynaptic element is
entirely dependent on the receptor protein. If there is no
receptor protein in the membrane of the postsynaptic element,
then the neurotransmitter has no effect. The depolarizing (more
likely to reach an action potential) or hyperpolarizing (less
likely to reach an action potential) effect is also dependent on
the receptor. When acetylcholine binds to the nicotinic receptor,
the postsynaptic cell is depolarized. However, when
acetylcholine binds to the muscarinic receptor, it might cause
depolarization or hyperpolarization of the target cell.
The amino acid neurotransmitters (glutamate, glycine, and
GABA) are almost exclusively associated with just one effect.
Glutamate is considered an excitatory amino acid because Glu
receptors in the adult cause depolarization of the postsynaptic
cell. Glycine and GABA are considered inhibitory amino acids,
again because their receptors cause hyperpolarization, making
the receiving cell less likely to reach an action potential.
The Right Dose
Sometimes too little or too much of a neurotransmitter may
affect an organism’s behavior or health. The underlying cause
of some neurodegenerative diseases, such as Parkinson’s
disease, appears to be related to over accumulation of proteins,
which under normal circumstances would be regulated by the
presence of dopamine. On the other hand, when an excess of the
neurotransmitter dopamine blocks glutamate receptors,
disorders like Schizophrenia can occur.
Neural Networks
Neural networks consist of a series of interconnected neurons,
and serve as the interface for neurons to communicate with each
other.
Key Points:
· The connections between neurons form a highly complex
network through which signals or impulses are communicated
across the body.
· The basic kinds of connections between neurons are chemical
synapses and electrical gap junctions, through which either
chemical or electrical impulses are communicated between
neurons.
· Neural networks are primarily made up of axons, which in
some cases deliver information as far as two meters.
· Networks formed by interconnected groups of neurons are
capable of a wide variety of functions. In fact the range of
capabilities possible for even small groups of neurons are
beyond our current understanding.
· Modern science views the function of the nervous system both
in terms of stimulus -response chains and in terms of
intrinsically generated activity patterns within neurons.
· Cell assembly, or Hebbian theory, asserts that “cells that fire
together wire together,” meaning neural networks can be created
through associative experience and learning.
Key Terms:
· cell assembly: Also referred to as Hebbian theory; the concept
that “cells that fire together wire together,” meaning neural
networks can be created through associative experience and
learning.
· action potential: A short-term change in the electrical
potential that travels along a cell such as a nerve or muscle
fiber, and allows nerves to communicate.
· plasticity: The ability to change and adapt over time.
A neural network (or neural pathway) is the interface through
which neurons communicate with one another. These networks
consist of a series of interconnected neurons whose activation
sends a signal or impulse across the body.
Neural networks: A neural network (or neural pathway) is the
complex interface through which neurons communicate with one
another.
See top of Lecture. Perhaps now you can begin to appreciate
the path breaking research of Ramón y Cajal.
As a child he was transferred many times from one school to
another because of behavior that was declared poor, rebellious,
and showing an “anti-authoritarian attitude.” An extreme
example of his precociousness and rebelliousness at the age of
eleven is his 1863 imprisonment for destroying his neighbor's
yard gate with a homemade cannon.
He and Camillo Golgi received the Nobel Prize in Physiology or
Medicine in 1906. Ramón y Cajal was the first person of
Spanish origin to win a Nobel Prize.
SUMMARY of LECTURE 9
The connections between neurons form a highly complex
network. The basic kinds of connections between neurons are
chemical synapses and electrical gap junctions, through which
either chemical or electrical impulses are communicated
between neurons. The method through which neurons interact
with neighboring neurons usually consists of several axon
terminals connecting through synapses to the dendrites on other
neurons.
If a stimulus creates a strong enough input signal in a nerve
cell, the neuron sends an action potential and transmits this
signal along its axon. The axon of a nerve cell is responsible for
transmitting information over a relatively long distance, and so
most neural pathways are made up of axons. Some axons are
encased in a lipid-coated myelin sheath, making them appear a
bright white; others that lack myelin sheaths (i.e., are
unmyelinated) appear a darker beige color, which is generally
called gray.
The process of synaptic transmission in neurons: Neurons
interact with other neurons by sending a signal, or impulse,
along their axon and across a synapse to the dendrites of a
neighboring neuron.
Some neurons are responsible for conveying information over
long distances. For example, motor neurons, which travel from
the spinal cord to the muscle, can have axons up to a meter in
length in humans. The longest axon in the human body is almost
two meters long in tall individuals and runs from the big toe to
the medulla oblongata of the brain stem.
The Capacity of Neural Networks
The basic neuronal function of sending signals to other cells
includes the capability for neurons to exchange signals with
each other. Networks formed by interconnected groups of
neurons are capable of a wide variety of functions, including
feature detection, pattern generation, and timing. In fact, it is
difficult to assign limits to the types of information processing
that can be carried out by neural networks. Given that
individual neurons can generate complex temporal patterns of
activity independently, the range of capabilities possible for
even small groups of neurons are beyond current understanding.
However, we do know that we have neural networks to thank for
much of our higher cognitive functioning.
Behaviorist Approach
Historically, the predominant view of the function of the
nervous system was as a stimulus-response associator. In this
conception, neural processing begins with stimuli that activate
sensory neurons, producing signals that propagate through
chains of connections in the spinal cord and brain, giving rise
eventually to activation of motor neurons and thereby to muscle
contraction or other overt responses. Charles Sherrington, in his
influential 1906 book The Integrative Action of the Nervous
System, developed the concept of stimulus-response
mechanisms in much more detail, and behaviorism, the school
of thought that dominated psychology through the middle of the
20th century, attempted to explain every aspect of human
behavior in stimulus-response terms.
Hybrid Approach
Experimental studies of electrophysiology, beginning in the
early 20th century and reaching high productivity by the 1940s,
showed that the nervous system contains many mechanisms for
generating patterns of activity intrinsically—without requiring
an external stimulus. Neurons were found to be capable of
producing regular sequences of action potentials (“firing”) even
in complete isolation. When intrinsically active neurons are
connected to each other in complex circuits, the possibilities for
generating intricate temporal patterns become far more
extensive. A modern conception views the function of the
nervous system partly in terms of stimulus-response chains, and
partly in terms of intrinsically generated activity patterns; both
types of activity interact with each other to generate the full
repertoire of behavior.
Hebbian Theory
In 1949, neuroscientist Donald Hebb proposed that simultaneous
activation of cells leads to pronounced increase in synaptic
strength between those cells, a theory that is widely accepted
today. Cell assembly, or Hebbian theory, asserts that “cells that
fire together wire together,” meaning neural networks can be
created through associative experience and learning. Since
Hebb’s discovery, neuroscientists have continued to find
evidence of plasticity and modification within neural networks.
CHE 102: LECTURE 7 FOSSIL FUELS
An oil refinery or petroleum refinery is an industrial plant
where crude oil is transformed and refined into more useful
products such as gasoline, diesel fuel, jet fuel, naptha, asphalt,
heating oil, kerosene, liquefied petroleum gas, and fuel oils.
Oil, coal, natural gas and other fossil fuels are called "fossil"
because these fuels are the preserved carbon-hydrogen remnants
of ancient life. Coal is formed from plants that decomposed and
accumulated in ancient swamps.
EXAMPLES: Fossil Fuels:
Coal: Coal is the primary fuel for the production
of electricity and is responsible for about 40% of the electric
power supply in the United States.
Oil: Oil is the primary source for the world's transportation.
Natural Gas: About 27% of U.S. energy is fueled by natural
gas. Natural gas is the cleanest burning fossil fuel.
CHEMISTRY: fossil fuel combustion.
One molecule of methane, combined with two oxygen
molecules, react to form a carbon dioxide molecule, and two
water molecules (usually given off as steam or water vapor)
releasing energy. See Lecture 3 and figure below.
COAL
Coal is a combustible black or brownish-black sedimentary
rock usually occurring in rock strata in layers or veins
called coal beds or coal seams. The harder forms, such
as anthracite coal, can be regarded as metamorphic rock because
of later exposure to elevated temperature and pressure.
NOTE: Geologists classify rocks into three main rock types.
Rocks are either a single mineral or a combinations of minerals.
Sedimentary rocks are a type of rock that formed by the
accumulation or deposition of small particles (minerals or
organic matter) at the Earth’s surface, subsequently followed
by their cementation on the floor of oceans or other bodies of
water. Examples: sandstone, limestone (see below).
Limestone is a carbonate sedimentary rock that is often
composed of the skeletal fragments of marine organisms such as
coral, foraminifera, and molluscs. Its major materials are the
minerals calcite (CaCO3).
and aragonite,
which are different crystal forms of calcium carbonate
(CaCO3).
Metamorphic rocks arise from the transformation of existing
rock types, in a process called metamorphism, which means
"change in form". The original rock is subjected to heat and
pressure, causing profound physical or chemical changes. The
precursor may be a sedimentary, igneous, or existing
metamorphic rock. Examples: slate, marble.
Marble is a metamorphic rock composed of recrystallized
carbonate minerals, most commonly calcite (see above) or
dolomite. In Geology, the term marble refers to metamorphosed
limestone. The Taj Mahal in the Indian city of Agra is entirely
clad in marble.I was amazed to find that the limestone in the Taj
Mahal structure is so transparent, the interior of this
architectural masterpiece is “illuminated.”
Igneous rock is formed through the cooling and solidification of
lava (or magma) from volcanic eruptions. The magma can be
derived from partial melts of existing rocks in either a planet's
mantle or crust. Example: obsidian, granite (see below).
The word "granite" comes from the Latin granum, a grain, in
reference to the coarse-grained structure of such a rock. Strictly
speaking, granite is an igneous rock with between 20% and 60%
quartz (See Lecture 4) by volume, and at least 35% of the total,
by feldspar [ Feldspar is an abundant rock-forming mineral
typically occurring as colorless or pale-colored crystals and
consisting of aluminum silicates of potassium, sodium, and
calcium] . A crystal of one form of feldspar shown below.
Coal is composed primarily of carbon, along with variable
quantities of other elements, chiefly hydrogen, sulfur, oxygen,
and nitrogen. Coal is a fossil fuel that forms when dead plant
matter is converted into peat, which in turn is converted
into lignite, then sub-bituminous coal, after that bituminous
coal, and lastly anthracite. Thus both biological and geological
processes are involved in its formation. The geological
processes take place over millions of years.
There are six main types of coal that are regularly used in
power plants or by other sectors of society:
Peat. Peat is formed from decaying vegetation, and is
considered to be the precursor of coal
Lignite.
Lignite is formed from compressed peat, and is often referred to
as brown coal
Bituminous/Sub Bituminous Coal
Steam Coal
Anthracite
Graphite
Coal
Sedimentary rock
Anthracite coal
Element Composition of Various types of Coal: Mass % of each
element.
type of coal C H O N S
lignite 71 4 23 1 1
subbituminous 77 5 16 1 1
bituminous 80 6 8 1 5
anthracite 92 3 3 1 1
NOTE: Anthracite is the “cleanest” coal, lignite the “dirtiest.”
Sources of Energy: fossil fuels (2007).
petroleum 36.0 %
coal 27.4 %
natural gas 23.0%
The following two account for 14.8%.
nuclear 8.5 %
hydroelectric 6.3 %
All of the following account for 0.9%.
geothermal
solar
tidal
wood
waste
Historical record of fossil fuel use: Wood Coal
Petroleum/Natural Gas Hydro/Nuclear
1850 91% 9%
1900 21% 71% 5%
3%
1950 6% 36% 52%
6%
1975 3% 18% 73%
6%
2000 4% 23% 62%
11%
The separation of petroleum into “fractions” (by length of
carbon chain) is what occurs in oil refineries.
C5 – C10 gasoline
C10 – C18 kerosene
C15 – C25 diesel fuel, heating oil, lubricating oil
> C25 asphalt
In the New York Times today (4/21/2020), the banner headline
is:
“Coronavirus Live Updates: Trump Says He Will Halt
Immigration; Oil Prices Crater, and Stocks Fall”
The oil market meltdown is continuing. Brent crude, the
international benchmark, was down about 18 percent, to $20.90
a barrel.
GREENHOUSE EFFECT: Overview
1. Solar radiation reaches the Earth's atmosphere - some of this
is reflected back into space.
2. The rest of the sun's energy is absorbed by the land and the
oceans, heating the Earth.
3. Heat radiates from Earth towards space.
4. Some of this heat is trapped by greenhouse gases in the
atmosphere, keeping the Earth warm enough to sustain life.
A greenhouse gas is a gas that absorbs and emits radiant energy
within the (thermal) infrared range. Greenhouse gases cause the
greenhouse effect on planets. Greenhouse gases include water
vapor, carbon dioxide, methane, nitrous oxide, ozone and some
artificial chemicals such as chlorofluorocarbons (CFCs). The
molecular structures of ozone and nitrous oxide are shown
below.
OZONE
NOTE: The ozone layer or ozone shield is a region of Earth's
stratosphere that absorbs most of the Sun's ultraviolet radiation.
The ozone layer contains a high concentration of ozone in
relation to other gases in the layer, although still small in
relation to gases (e.g. oxygen O2 and nitrogen N2 ) in other
regions of the stratosphere.
NITROUS OXIDE (“laughing gas”)
NOTE: Nitrous oxide has significant medical uses, especially
in surgery and dentistry, for its anaesthetic and pain reducing
effects. Its colloquial name "laughing gas", coined by
Humphry Davy (see Lecture 4 ), is due to the euphoric effects
upon inhaling it, a property that has led to its recreational use
as a dissociative anaesthetic ( A unique anesthesia characterized
by analgesia and amnesia with minimal effect on respiratory
function. The patient does not appear to be anesthetized and can
swallow and open eyes but does not process information). It is
also used as an oxidizer in rocket propellants and in motor
racing to increase the power output of engines.
5. Human activities such as burning fossil fuels, agriculture and
land clearing are increasing the amount of greenhouse gases
released into the atmosphere.
6. This results in trapping extra heat, and causing the Earth's
temperature to rise.
The greenhouse effect is a natural process that warms the
Earth’s surface.
Absorbed thermal energy warms the atmosphere and the surface
of the Earth. This process maintains the Earth’s temperature at
around 91.4 degrees Fahrenheit warmer than it would otherwise
be, allowing life on Earth to exist.
The problem we now face is that human activities – particularly
burning fossil fuels (coal, oil and natural gas), agriculture and
land clearing – are increasing the concentrations of greenhouse
gases. This is the enhanced greenhouse effect, which is
contributing to global warming, an overall increase in the
temperature of the Ear
Average global temperatures from 2010 to 2019 compared to a
baseline average from 1951 to 1978. Source: NASA.
CARBON FOOTPRINT
A carbon footprint is historically defined as the
total greenhouse gas (GHG) emissions caused by an individual,
event, organization, or product, expressed as carbon dioxide
equivalent.
Greenhouse gases, including the carbon-containing gases carbon
dioxide and methane, can be emitted through the burning of
fossil fuels, land clearance (e.g. in the Amazon basin) and the
production and consumption of food, manufactured goods,
materials, wood, roads, buildings, transportation and other
services.
In most cases, the total carbon footprint cannot be calculated
exactly because of inadequate knowledge of and data about the
complex interactions between contributing processes, including
the influence of natural processes that store or release carbon
dioxide. For this reason, the following definition of a carbon
footprint has been proposed:
Carbon Footprint: A measure of the total amount of carbon
dioxide (CO2) and methane (CH4) emissions of a defined
population, system or activity, considering all relevant sources,
sinks and storage within the spatial and temporal boundary of
the population, system or activity of interest.
Most of the carbon footprint emissions for the average U.S.
household come from "indirect" sources, e.g. fuel burned to
produce goods far away from the final consumer. These are
distinguished from emissions which come from burning fuel
directly in one's car or stove, commonly referred to as "direct"
sources of the consumer's carbon footprint.
The 100-year global warming potential (GWP100) is calculated
with reference to carbon dioxide.
Coal - Wikipedia
https://en.wikipedia.org/wiki/Coal
GLOBAL WARMING
Global warming - Wikipedia
en.wikipedia.org › wiki › Global_warming
ECONOMIC IMPLICATIONS
The Economic Impact of Greenhouse Gas Emissions | Clive Best
clivebest.com/?p=7139
LECTURE 9. From Alcohol and Aspirin to Hallucinogens
and Opioids
La Nuit Etoilée (The Starry Night) is an oil on canvas by Dutch
post-impressionist painter Vincent van Gogh (1853-1890).
Painted in June 1889, it describes the view from the east-facing
window of his asylum room at Saint-Rémy-de-Provence, just
before sunrise, with the addition of an ideal village. He spent a
long period in 1889-90 in a clinic because of his mental
instability, before committing suicide. You do not have to be a
chemist to wonder about the source of the swirls, spirals and
other strange effects. Van Gogh's instability and suicide have
been blamed on the liqueur-like drink absinthe, a fashionable
French beverage in the half century up to the first world war.
Absinthe, is a green liquid with an anise smell, made by
distilling a mixture of alcohol, herbs (notably wormwood) and
water. In the late 19th century, it became a national drink in
France. Fashionable among the artistic community, it became
cheap enough to be the spirit “beverage of choice” among the
poor.
Writers such as Baudelaire, Edgar Allan Poe and Verlaine relied
upon it, and a whole range of artists (Degas, Gauguin, Manet,
Picasso, Toulouse-Lautrec, and Van Gogh) are associated with
it, often for including it in their paintings. Known as la fée
verte (the green fairy), absinthe gave rise to l'heure verte, the
time (5 pm) when drinkers in all walks of life went to a café for
their absinthe, what we would now call a “Happy Hour”.
L'Absinthe
Artist
Edgar Degas
Year
1875–76
We begin by considering alcoholic beverages and their effect on
the brain.
How does alcohol affect the brain?
Alcohol has a profound effect on the complex structures of the
brain. It blocks chemical signals between brain cells (neurons),
leading to the common intermediate symptoms of intoxication,
including impulsive behavior, slurred speech, poor memory, and
slowed reflexes.
If heavy drinking continues over extended periods of time, the
brain adopts to the blocked signals by responding more
dramatically to certain brain chemicals, the neurotransmitters.
After alcohol leaves the system, the brain continues over-
activating the neurotransmitters, causing painful and potentially
dangerous withdrawal symptoms that can damage brain cells.
This damage is made more acute by “binge drinking” and
sudden withdrawal.
Alcohols damage to the brain can take several forms. The first
is neurotoxicity, which occurs when neurons over react to
neurotransmitters for too long. Too much exposure to a
neurotransmitter can cause neurons to eventually “burn out.”
Since neurons make up the pathways between different parts of
the brain, when they begin “burning out,” it can cause
noticeable slowing in the response of these pathways. People
with alcohol dependence often experience “brain shrinkage,”
which is reduced volume of both gray matter (cell bodies) and
white matter (cell pathways) over time.
There are some subtle differences in how brain damage occurs
in men and women, but regardless of gender, loss of brain
matter increases with age and amount of alcohol consumed.
What are the observable effects of this damage?
Since alcohol affects a large portion of the brain, many different
kinds of cognitive impairment can occur as a result of heavy
drinking, including problems with verbal fluency and verbal
learning, processing speed, working memory, attention, problem
solving, spatial processing and impulsivity.
Parts of the brain relating to memory and “higher functions” (
for example, problem solving and impulse control) are more
susceptible to damage than other parts of the brain, so problems
in these areas tend to be worse than others. Adolescents are
especially at risk for long-lasting or permanent damage and
performance deficits, since their most-impacted areas of the
brain are still in development.
Without treatment, cognitive impairment grows worse,
eventually developing into a lasting syndrome known as alcohol
related dementia. This syndrome represents about 10% of all
dementia cases (additionally, alcohol is estimated to contribute
to roughly 29% of all other dementia cases).
Cognitive deficits are made worse by malnutrition, especially a
deficiency of vitamin B (a common deficiency in alcohol-
dependent individuals). Malnutrition and heavy alcohol
consumption can cause serious impairments in memory and
language over time and can potentially result in permanent
cognitive disorder called Wernicke-Korsakoff syndrome, which
causes amnesia and can lead to coma if left untreated.
In Lecture 5, we commented on the different physiological
effects induced by methanol and ethanol.
methanol
and ethanolMethanol is a highly toxic alcohol with a smell and
taste similar to ethanol. Small amounts (around 50 - 100 ml )
cause permanent blindness and severe neurological dysfunction
leading to death. More than half of methanol-related morbidity
and mortality is classified as accidental and therefore
preventable. In addition, it can be suicidal by ingestion of a
variety of commercial paint thinners, gasoline anti-freeze,
windshield products, organic solvents, shellac varnish, washer
fluid, photocopying fluids, perfumes, and in some eau de
cologne. Occasionally, it is due to the fraudulent adulteration of
wine or other alcoholic beverages. Its ingestion causes high
anion gap metabolic acidosis from the production of formic and
lactic acids and central nervous system disturbances ranging
from inebriation and drowsiness to obtundation (A condition in
which the senses have been dulled by trauma, mistreatment, or
psychological stress.), seizure and coma.
Aspirin
The active ingredient in aspirin is acetylsalicylic acid, C9 H8
O4 .
This organic acid was found in leaves from the willow tree, and
has been used for its health effects for at least 2,400 years.
Medicines made from willow and other salicylate-rich plants
appear in clay tablets from ancient Sumer as well as the Ebers
papyrus from ancient Egypt. Hippocrates (around 400 BC)
referred to the use of salicylic tea to reduce fevers.
Aspirin has been manufactured since 1899 by the German
company Bayer.
There are many generic varieties of aspirin. A generic
drug manufacturer must prove that their product contains the
same active ingredient(s) as the brand name product.
Aspirin can be used to fight a host of health problems: cerebral
thromboses (with less than one tablet a day); general pain or
fever (two to six tablets a day); and diseases such as rheumatic
fever, gout, and rheumatoid arthritis. The drug is also beneficial
in helping to ward off heart attacks. In addition, biologists use
aspirin to interfere with white blood cell action, and molecular
biologists use the drug to activate genes.
The wide range of effects that aspirin can produce made it
difficult to pinpoint how it actually works, and it wasn't until
the 1970s that biologists hypothesized that aspirin and related
drugs (such as ibuprofen) work by inhibiting the synthesis of
certain hormones that cause pain and inflammation. [Hormones
are regulatory substances produced in an organism and
transported in tissue fluids such as blood or sap to stimulate
specific cells or tissues into action.] Since then, scientists have
made further progress in understanding how aspirin works. They
now know, for instance, that aspirin and its relatives actually
prevent the growth of cells that cause inflammation.
As a further example of how a change in a single functional
group (See Lecture 5) can change the chemical, physical and
physiological properties of a molecule, note that both aspirin
and oil of wintergreen are synthesized from the same precursor,
salicilic acid. See structure and reactions below.
Autonomic nervous system drugs
The autonomic nervous system controls the involuntary
processes of the glands, large internal organs, cardiac muscle,
and blood vessels. It is divided functionally and anatomically
into the sympathetic and the parasympathetic systems, which
are associated with the fight-or-flight response or with rest and
energy conservation, respectively.
Organization of the autonomic nervous system.Encyclopædia
Britannica, Inc.
Modern pharmacological understanding of the autonomic
nervous system emerged from several key insights made in the
early 20th century. The first of these came in 1914, when
British physiologist Sir Henry Dale suggested that
acetylcholine was the neurotransmitter at the synapse between
preganglionic and postganglionic sympathetic neurons and also
at the ends of postganglionic, parasympathetic nerves.
Preganglionic neurons originate in the central nervous system,
whereas postganglionic neurons lie outside the central nervous
system.
Dale showed that acetylcholine could produce many of the same
effects as direct stimulation of parasympathetic nerves. Firm
evidence that acetylcholine was in fact the neurotransmitter
emerged in 1921, when German physiologist Otto Loewi
discovered that stimulation of the autonomic nerves to the heart
of a frog caused the release of a substance, later identified to be
acetylcholine, which slowed the beat of a second heart perfused
with fluid from the first. Similar direct evidence of the release
of a sympathetic neurotransmitter, later shown to be
norepinephrine (noradrenaline), was obtained by American
physiologist Walter Cannon in 1921.
Norepinephrine
Both acetylcholine and norepinephrine act on more than one
type of receptor. Dale found that two foreign
substances, nicotine and muscarine, could each mimic some,
but not all, of the parasympathetic effects of acetylcholine.
The structure of muscarine is given below, that of nicotin later
in this Lecture.
Muscarine
Nicotine stimulates skeletal muscle and sympathetic ganglia
cells. Muscarine stimulates receptor sites located only at the
junction between postganglionic parasympathetic neurons and
the target organ. Muscarine slows the heart, increases the
secretion of body fluids, and prepares the body for digestion.
Dale therefore classified the many actions of acetylcholine into
nicotinic effects and muscarinic effects. Drugs that influence
the activity of acetylcholine, including atropine, scopolamine,
and tubocuraine, are known as cholinergic drugs (see later text).
A similar analysis of the sympathetic effects of norepinephrine,
epinephrine, and related drugs was carried out by American
pharmacologist Raymond Ahlquist, who suggested that these
agents acted on two principal receptors. A receptor that is
activated by the neurotransmitter released by an adrenergic
neuron is said to be an adrenoceptor. Ahlquist called the two
kinds of adrenoceptor alpha (α) and beta (β). This theory was
confirmed when Sir James Black developed a new type of drug
that was selective for the
β-adrenoceptor.
Adrenoline is a hormone secreted by the adrenal glands,
especially in conditions of stress, increasing rates of blood
circulation, breathing, and carbohydrate metabolism and
preparing muscles for exertion.
α-adrenoceptors and β-adrenoceptors are divided into
subclasses: α1 ,α2 and β1, β2, β3.
These receptor subtypes were recognized by their responses to
specific agonists and antagonists, which provided important
leads for the development of new drugs. For example,
salbutamol was discovered as a specific β2-adrenoceptor
agonist. It is used to treat asthma and is a great improvement
over its predecessor, isoproterenol. Because the activity of
isoproterenol is not specific, it acts on β1-adrenoceptors as well
as β2-adrenoceptors, resulting in cardiac effects that are
sometimes dangerous. Salbutamol and other agents that act on
adrenoceptors, including albuterol, ephedrine, and imipramine,
are known as adrenergic drugs.
Central nervous system drugsSeveral major groups of drugs,
notably anethetics and psychiatric drugs, affect the central
nervous system. These agents often are administered in order to
produce changes in physical sensation, behavior, or mental
state.
General anesthetics induce a temporary loss of consciousness,
enabling surgeons to operate on a patient without the patient’s
feeling pain.
Local anesthetics induce a loss of sensation in just one area of
the body by blocking conduction in nerves at and near the
injection site.Drugs that influence the operation of
neurotransmitter systems in the brain can profoundly influence
and alter the behavior of patients with mental disorders.
Psychiatric drugs that affect mood and behavior may
be classified as antidepressants, antianxiety agents,
antipsychotics or antimanics.
What is a hallucinogen?
A hallucinogen is a psychoactive agent that often causes
hallucinations, perceptual anomalies, and other substantial
subjective changes in thought, emotion, and consciousness that
are not typically experienced to such degrees with other
categories of drugs. Research suggests that
classic hallucinogens work at least partially by temporarily
disrupting communication between brain chemical systems
throughout the brain and spinal cord.
Some hallucinogens interfere with the action of
the brain chemical serotonin, which regulates mood and sensory
perception.
Serotonin
What are some common hallucinogens?
Caffine
Caffeine is a central nervous system (CNS) stimulant. It is the
world's most widely consumed psychoactive drug. Unlike many
other psychoactive substances, it is legal and unregulated in
nearly all parts of the world. There are several known
mechanisms to explain the effects of caffeine. The most
prominent is that it reversibly blocks the action of adenosine
on its receptors and consequently prevents the onset of
drowsiness induced by adenosine. Caffeine also stimulates
certain portions of the autonomic nervous system.
Nicotine
Nicotine is a stimulant (alkaloid) that is naturally produced in
the nightshade family of plants. It is highly addictive. Nicotine
acts as a receptor agonist at most nicotinic acetylcholine
receptors, except at two nicotinic receptor subunits where it acts
as a receptor antagonist.
Marijuana (Cannabis)
Marijuana is a psychoactive drug from the Cannabis plant used
primarily for medical or recreational purposes. The main
psychoactive component of cannabis is tetrahydrocannabinol,
which is one of the 483 known compounds in the plant,
including at least 65 other cannabinoids.
Cocaine
Cocaine, also known as coke, is a strong stimulant. Mental
effects may include loss of contact with reality, an intense
feeling of happiness or agitation. Physical symptoms may
include a fast heart rate, sweating and large pupils. High doses
can result in very high blood pressure or body
temperature. Effects begin within seconds to minutes of use
and last between five and ninety minutes. Cocaine has a small
number of accepted medical uses such a numbing and
decreasing bleeding during nasal surgery.
Cocaine is addictive due to its effect on the reward pathway in
the brain.
Colombia, Peru and Bolivia are the most important cocaine-
producing countries.
What is an opioid?
Opioids are substances that act on opioid receptors to
produce morphine-like effects. Medically they are primarily
used for pain relief, including anesthesia. Other medical uses
include suppression of diarrhea, replacement therapy for opioid
use disorder, reversing opioid overdose, suppressing cough, as
well as for executions in the US. Extremely potent opioids such
as carfentanil are approved only for veterinary use. Opioids are
also frequently used non-medically for their euphoric effects or
to prevent withdrawal.
Side effects of opioids may include: itchiness, sedation,
respiratory depression, constipation, and euphoria. Long-term
use can cause tolerance, meaning that increased doses are
required to achieve the same effect, and physical dependence,
meaning that abruptly discontinuing the drug leads to
unpleasant withdrawal symptoms. The euphoria attracts
recreational use and frequent, escalating recreational use of
opioids typically results in addiction. An overdose or concurrent
use with other depressant drugs like benzodiazepine commonly
results in death from respiratory depression.
Opioids act by binding to opioid receptors, which are found
principally in the central and peripheral nervous system and the
gastrointestinal tract. These receptors mediate both the
psychoactive and the somatic effects of opioids. Opioid drugs
include partial agonists, like the anti-diarrhea drug loperamide
and atagonists like naloxegol for opioid-induced constipation,
which do not cross the blood-brain barrier but can displace
other opioids from binding to those receptors.
What are some examples of opioids?
Morphine
Morphine is found naturally in a number of plants and animals,
including humans. It acts directly on the central nervous
system (CNS) to decrease the feeling of pain. It can be taken
for both acute pain and chronic pain. It is frequently used for
pain from myocardial infarction and during labor. After
injection, maximum effect is reached after about 20 minutes
when given intravenously and after 60 minutes when given by
mouth, while duration of effect is 3–7 hours.
Potentially serious side effects include decreased respiratory
effort and low blood pressure. Morphine is addictive and prone
to abuse.
Heroin
Heroin is a highly addictive drug processed from morphine, a
naturally occurring substance extracted from the seed pod of
certain varieties of poppy plants.Common side effects
include decreased breathing, dry mouth, drowsiness, impaired
mental function, constipation, and addiction. Side effects of
use by injection can include abscesses, infected heart valves and
pneumonia.Opium (or “poppy tears”, scientific
name: Lachryma papaveris) is dried latex obtained from the
seed capsules of the opium poppy Papaver somniferum.
Opium poppy seed pod exuding latex from a cu
Approximately 12 percent of opium is made up of morphine,
which is processed chemically to produce heroin and other
synthetic opioids for medicinal use and for illegal drug trade.
The latex also contains the closely related opiates codeine, and
non-analfesic alkaloids such as papaverine and noscapine.The
super sleuth, Sherlock Holmes (Robert Downey Jr. in the
movies), occasionally used addictive drugs, especially in the
absence of stimulating cases. He sometimes used morphine and
other times cocaine. Both drugs were legal in 19th-century
England. His sidekick, Dr. John Watson (Jude Law), strongly
disapproved of his friend's cocaine habit, describing it as the
detective's only vice, and was concerned about its effect on
Holmes's mental health and intellect.
Carfentanil
Loperamide
Naloxegol

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  • 1. CHE 102: LECTURE 8 From the Hydrogen Bond to the Blue Planet to Jurassic Park A 99-million-year old piece of amber discovered in 2016 by Lida Xing in Myanmar (Burma). Suspended inside is the skull of the smallest known bird, and, therefore, dinosaur, ever discovered. The dinosaur’s skull is only a little more than half an inch, from its beak to the end of its skull. The animal had bulbous eyes that looked out from the sides of its head, rather than straight ahead like the eyes of an owl or a human. HYDROGEN BOND A hydrogen bond (often abbreviated H-bond) is a type of intermolecular bonding between a hydrogen atom and a “lone pair” of electrons on an electron rich donor atom [particularly the second-row elements N, O or F, and hydrogen]. Such an interacting system is generally denoted Dn–H···Ac [Dn for donor, Ac for accepter] where the solid line signals a polar covalent bond, and the dotted or dashed line indicates the hydrogen bond. While hydrogen bonding has both covalent and electrostatic (ionic) contributions, present evidence suggests that the primary contribution is covalent. Hydrogen bonds can be intermolecular (occurring between separate molecules) or intramolecular or (occurring among parts of the same molecule). Examples of both will be given below. Depending on the nature of the donor and acceptor atoms which constitute the bond, and the geometry and local environment, the energy of a hydrogen bond can vary between 1 and 40
  • 2. kcal/mol. This makes them somewhat stronger than nonpolar (van der Waals) interactions, but weaker than fully covalent or ionic bonds. Roughly speaking, the energy of a H-bond is about 5-10% the energy of a covalent bond. This type of bond can occur in inorganic molecules such as water and in organic molecules like proteins and DNA (see later discussion). The hydrogen bond is responsible for many of the anomalous physical and chemical properties of compounds of N, O, and F. For example, intermolecular hydrogen bonding is responsible for the high boiling point of water (100 °C) compared to other hydrides that have much weaker hydrogen bonds. Intramolecular hydrogen bonding plays an important role in the structure of polymers, both synthetic and natural. It is also partly responsible for the secondary and tertiary structures of proteins and nucleic acids. H-BONDS: WATER Water is absolutely essential for our existence on Earth and plays a pivotal role in physics, chemistry, biology and geoscience. What makes water unique is not only its ubiquitous presence on Earth but also the anomalous behavior of many of its macroscopic properties. The density, specific heat, viscosity and compressibility of water behave in ways opposite to other liquids that we know. In a glass of ice water, everything is, in a sense, upside down. Strangely for the liquid state, water which freezes at 0 oC is the densest at 4 ˚C, and therefore stays on the bottom. This is why life can exist at the bottom of a lake and an ocean during winter, even when the surface is frozen. At a more prosaic level, this “inversion” in behavior is the reason why an ice cube floats at the top of a glass of ice tea. At the molecular level, the origin of this strange behavior, unique to water among the important liquids, is still a subject of
  • 3. great interest in physics and chemistry. The crystal structure of solid water (ice) was shown in Lecture 4 . See also the graphic below. Notice that, accounting for both covalent and H-bonds in water, a crystal of ice has a hexagonal symmetry, which is why snowflakes have a hexagonal symmetry. A snowflake is a single ice crystal that has achieved a sufficient size (either “by itself” or amalgamated with others) and falls through the Earth’s atmosphere as snow. In supersaturated air masses of water droplets in a cloud, each snowflake nucleates around a dust particle, freezing and accreting in crystal form. Complex shapes emerge as the flake moves through differing temperature and humidity zones in the atmosphere, so that individual snowflakes differ in detail from one another. They are categorized in eight broad classifications and at least 80 individual variants. The main constituent shapes for ice crystals, from which combinations may occur, are needle, column, plate, and rime. Snow appears white in color despite being made of clear ice. This is due to diffuse reflection of the whole spectrum of light by the small crystal facets of snowflakes.
  • 4. THE BLUE PLANETThe origin of water on Earth is the subject of an extensive body of research in the fields of planetary science, astronomy and astrobiology. Earth is unique among the rocky planets in the Solar System in that it is the only planet known to have oceans of liquid water on its surface. Liquid water, which is necessary for life, continues to exist on the surface of Earth because the planet is at a distance far enough from the Sun that it does not lose its water to the greenhouse effect, but not so far that low temperatures cause all water on the planet to freeze. Earth could not have condensed from the protoplanetary disk with its current oceans of water because the early inner Solar System was far too hot for water to condense. Instead, water and other volatiles must have been delivered to Earth from the Solar System later in its history. Modern geochemical evidence suggests that water was delivered to Earth by impacts from icy planetesimals similar in composition to modern asteroids in the outer edges of the asteroid belt. WATER: Essential for Life on Earth Living System Water is fundamental to the survival of organisms. Doctors recommend drinking 8 cups of water a day in order to maintain a healthy lifestyle. Clean water is one of the primary concerns of all countries, especially Third World countries. Wars have
  • 5. been fought over who gets the rights to drink from the source of water. Recall the movie, “Lawrence of Arabia.” Wars in the future will likely not be fought over oil or mineral resources, but water. Why is this substance so vital to the survival of all life? First, liquid water is essential for biochemical reactions by providing a medium which facilitates the transport of vital nutrients from one place to another within a cell. Second, water, as a polar molecule, is considered the “universal solvent”, in that everything dissolves in water to some degree, allowing nutrients to be integrated into water with relative ease. NOTE: The solvent properties of water or other substances is summed up in the simple phrase “Like dissolves like.” Table salt, which is composed of Na+ and Cl- ions, dissolves readily in water, a polar molecule. Salad dressing, oil and vinegar, left standing, will separate into a vinegar (polar) phase and an oil (nonpolar) phase. You have to shake the bottle to mix the two (which then forms an emulsion). Additives aside, gasoline is composed of the nonpolar hydrocarbon molecule octane (C8H18). Octane
  • 6. When filling up your gas tank, if you happen to spill gas on a wet pavement you may have noticed technicolor fringes. These result because gasoline and water don’t mix. Water has a higher density than octane (0.993 g/cm3 vs 0.706 g/cm3), so the gas floats on top. This thin film of oil, refracted by sunlight, produces the “rainbow” fringes. In understanding the d=3 dimensional structure of proteins (See Lecture 6), amino acids with polar side chains “stick out” into the aqueous medium of a cell, whereas amino acids with nonpolar side chains are buried away inside the structure. This sequestering of nonpolar amino acids in the interior of a protein was analyzed in 1953 by my PhD advisor at Princeton, Walter Kauzmann, who baptized the effect “hydrophobic bonding.” Today, the hydrophobic effect is discussed extensively in standard textbooks on biochemistry and cell biology. Third, water also helps enzymes to function [Recall, enzymes are proteins that catalyze chemical reactions, thus speeding up the reaction. See Lecture 6]. Another unique thing about water is that all three states (liquid, solid and gas) exists naturally in nature. [Remember Thales? See Lecture 1] This allows the water cycle to occur in nature, which replenishes water around the world. Pure water has a wide range of temperature between its freezing and boiling points (100 oC). Both temperatures can be manipulated with salt and other minerals.
  • 7. Water has a very high specific heat, which means it takes a lot of energy to heat it up. This allows water to survive the intense heat variations that Earth has without evaporating at once, and helps to moderate the temperature of the planet thanks to the oceans. As noted above, a remarkable characteristic of water is that when it turns into solid ice, it expands instead of contracts, unlike a normal solid. The result is that ice floats above liquid water, thus preventing it from displacing water and causing the ocean levels to rise, and also allowing Arctic and Antarctic life to thrive. H-BONDS: The α-Helix in Proteins and the Double Helix in Nucleic Acids The alpha helix (α-helix) in the secondary structure of proteins is a right-hand helix in which every N-H group in one amino acid (residue) H-bonds to the C=O group of an amino acid located three or four residues earlier along the sequence of amino acids making up the protein. The alpha helix is called a Pauling–Corey–Branson α-helix. The name 3.613 helix is also used for this type of helix, specifying the average number of amino acids (residues) per helical turn, with 13 atoms being involved in the ring formed by the hydrogen bond. See below. H-bonds break when a protein is subject to increased temperature. This is what happens when you fry an egg for breakfast. The egg white will quickly turn from clear and runny to white and firm. Heat energy agitates the egg-white proteins, making them bounce around and hit water molecules and other
  • 8. proteins. These collisions break the weak H-bonds that held the protein curled up in its “native state”, allowing the chain of amino acids to partly unfold – a process called denaturation. When these agitated proteins bump against one another, new and stronger chemical bonds form between them. As these proteins join together in an interconnected web, the egg white congeals into a solid, and you have a “sunny side up egg.” Hydrogen bonds are also responsible for specific base-pair formation in the DNA double helix (See Lecture 6) and a major contributor to the stability of the DNA double helix structure. A hydrogen-bond donor includes the hydrogen atom and the atom with which it is most tightly linked . In genetics, DNA replication is the process by which DNA makes a copy of itself during cell division. The first step in DNA replication is to 'unzip' the double helix structure of the DNA molecule. H-bonds between base pairs (See Lecture 6) are broken and the two separated strands then act as templates for making new strands of DNA. EVOLUTION of LIFE on EARTH: AGE of the DINOSAURS Dinosaurs are a diverse group of reptiles. They first appeared during the Triassic period, between 243 and 233.23 million years ago. They became the dominant terrestrial vertibrates after the Triassic-Jurassic extinction event 201.3 million years
  • 9. ago. Their dominance continued through the Jurassic and Cretaceous periods. The fossil record demonstrates that birds are modern feathered dinosaurs (See top of Lecture), having evolved during the Late Jurassic epoch. Indeed, birds were the only dinosaur lineage to survive the Cretaceous-Palogene extinction event approximately 66 million years ago. The Chicxulub crater is an impact crater buried underneath the Yucatán Peninsula in Mexico. It was formed when a large asteroid or comet about 6.8 to 50.3 miles in diameter, struck the Earth. The date of the impact coincides precisely with the Cretaceous-Paleogene boundary (commonly known as the "K–Pg boundary" ), slightly less than 66 million years ago, and a widely accepted theory is that worldwide climate disruption from the event was the cause of the a mass extinction in which 75% of plant and animal species on Earth became extinct. Dinosaurs can be divided into avian dinosaurs, or birds; and non-avian dinosaurs, which are all dinosaurs other than birds. The non-avian dinosaurs didn’t survive. AMBER Amber, fossilized tree resin, has long been appreciated for its color and natural beauty. Much valued from antiquity to the present as a gemstone, amber has also been made into a variety of decorative objects. Below is the Amber Room in the Catherine Palace in Saint Petersburg, the Russian port on the Baltic Sea, founded by the Czar Peter the Great in 1703.
  • 10. A town (Amer or Amber) in Rajasthan, India, founded around 1036, is famous for its Amber Fort. Ganesh Pol Entrance My work with the World Bank and the International Institute of Theoretical and Applied Physics took me to many parts of the World. I’ve seen both of the above, and they are stunning. Insects trapped in tree resin, became “fossilized.” The science underlying Jurassic Park is that the DNA isolated from a dinosaur trapped in tree resin, and then fossilized, can be extracted using standard techniques in biochemistry and used to create “the original.” Lastly, from at least the 16th century BC, amber was transported from Northern Europe to the Mediterranean region. Recalling Lecture 1, the breast ornament of the Egyptian pharaoh Tutankhamen (c. 1333–1324 BC) contains large amber beads from the Baltic Sea area (today’s Poland). Amber was sent from the North Sea to the temple of Apollo at Delphi as an offering. Ancient trade routes in Asia (the Silk Road) brought amber from the Black Sea to China, where it was customary to burn amber during large festivities. Below is an expensive decorative object made of rare white amber, an artist’s representation of the Great Wall of China
  • 11. (also a “must see”). LECTURE 99From Neurons to the Nervous System to the Brain The neuron's place as the primary functional unit of the nervous system was first recognized in the late 19th century by the Spanish anatomist Santiago Ramón y Cajal (1852-1934), a neuroscientist and pathologist specializing in neuroanatomy and, especially, the central nervous system. In 1888 Ramón y Cajal published a paper about the pigeon cerebellum. In this paper, he stated that he could not find evidence for cross connections (anastomosis) between axons and dendrites and called each nervous element "an absolutely autonomous canton." This became known as the neuron doctrine, one of the central tenets of modern neurobiology. Above is his 1899 drawing of neurons in the pigeon cerebellum. This Lecture focuses on the chemistry of neurons, specialized cells that transmit chemical and electrical signals to facilitate communication between the brain and the body. In learning about a new field, one can get befuddled very quickly with the jargon used by experts in the field and get lost, not being able “to see the forest for the trees.” So, before each section, I give a summary of Key Points and Key Terms you will need to understand that section. At the expense of “over kill,” I have repeated earlier “points” and “terms” at subsequent points in the Lecture so that you won’t have to “backtrack” to figure out what is going on.
  • 12. Neurons are specialized cells that transmit chemical and electrical signals in the brain. They are the basic building blocks of the central nervous system. Key Points: · Neurons are specialized cells that transmit chemical and electrical signals in the brain; they are the basic building blocks of the central nervous system. · The primary components of the neuron are the soma (cell body), the axon (a long slender projection that conducts electrical impulses away from the cell body), dendrites (tree- like structures that receive messages from other neurons), and synapses (specialized junctions between neurons). · Some axons are covered with myelin, a fatty material that acts as an insulator and conductor to speed up the process of communication. · Sensory neurons are neurons responsible for converting external stimuli from the environment into corresponding internal stimuli. · Motor neurons are neurons located in the central nervous system (CNS); they project their axons outside of the CNS to directly or indirectly control muscles. · Interneurons act as the “middle men” between sensory and motor neurons, which convert external stimuli to internal stimuli and control muscle movement, respectively. Key Terms: · glial cell: Non-neuronal cells that provide structure and support to neurons. · synapse: The junction between the terminal of a neuron and either another neuron or a muscle or gland cell, over which nerve impulses pass. · myelin: A white, fatty material composed of lipids and lipoproteins that surrounds the axons of nerves and facilitates swift communication. · nodes of Ranvier: Periodic gaps in the myelin sheath where the signal is recharged as it moves along the axon.
  • 13. The neuron is the basic building block of the brain and central nervous system. The brain is made up entirely of neurons and glial cells. Nearly 86 billion neurons work together within the nervous system to communicate with the rest of the body. Fun facts: The Milky Way galaxy has an estimated 100 billion stars. It is estimated that there are 10 trillion galaxies in the observable universe. Multiplying that by the Milky Way's estimated 100 billion stars results in a large number indeed: 1,000,000,000,000,000,000,000,000 stars. Given this astronomically-large value, the probability that there is (at least) one star with a planet “just the right distance” from that star is quite high. Whether there are large bodies of H2O on this planet is another matter but, if so, assuming the same distribution of elements as on planet Earth, the chemistry of Carbon can kick in and life on that planet is possible. Neurons are responsible for consciousness and thought to pain and hunger. You need almost as many neurons to function as there are stars in our Milky Way. Structures of a Neuron In addition to having all the normal components of a cell (nucleus, organelles, etc.), neurons also contain unique structures for receiving and sending the electrical signals that make neuronal communication possible. The structure of a neuron: The above image shows the basic structural components of an average neuron, including the dendrite, cell body, nucleus, Node of Ranvier, myelin sheath, Schwann cell, and axon terminal. Dendrite Dendrites are branch-like structures extending away from the
  • 14. cell body, and their job is to receive messages from other neurons and allow those messages to travel to the cell body. Although some neurons do not have any dendrites, other types of neurons have multiple dendrites. Dendrites can have small protrusions called dendritic spines, which further increase surface area for possible connections with other neurons. Cell Body Like other cells, each neuron has a cell body (or soma) that contains a nucleus, smooth and rough endoplasmic reticulum, Golgi apparatus, mitochondria, and other cellular components. Axon An axon is a tube-like structure that carries an electrical impulse from the cell body (or from another cell’s dendrites) to the structures at opposite end of the neuron—axon terminals, which can then pass the impulse to another neuron. The cell body contains a specialized structure, the axon hillock, which serves as a junction between the cell body and the axon. Synapse The synapse is the chemical junction between the axon terminals of one neuron and the dendrites of the next. It is a gap where specialized chemical interactions can occur, rather than an actual structure. Function of a Neuron The specialized structure and organization of neurons allows them to transmit signals in the form of electric impulses from the brain to the body and back. Individually, neurons can pass a signal all the way from their own dendrites to their own axon terminals. At a higher level, neurons are organized in long chains, allowing them to pass signals very quickly from one to the other. One neuron’s axon will connect chemically to another neuron’s dendrite at the synapse between them. Electrically charged chemicals flow from the first neuron’s axon to the second neuron’s dendrite, and that signal will then flow from the second neuron’s dendrite, down its axon, across a synapse, into a third neuron’s dendrites, and so on.
  • 15. This is the basic chain of neural signal transmission, which is how the brain sends signals to the muscles to make them move, and how sensory organs send signals to the brain. It is important that these signals can happen quickly, and they do. Think of how fast you drop a hot potato—before you even realize it is hot. This is because the sense organ (in this case, the skin) sends the signal “This is hot!” to neurons with very long axons that travel up the spine to the brain. If this didn’t happen quickly, people would burn themselves. Other Structures Dendrites, cell bodies, axons, and synapses are the basic parts of a neuron, but other important structures and materials surround neurons to make them more efficient. Myelin Sheath Some axons are covered with myelin, a fatty material that wraps around the axon to form the myelin sheath. This external coating functions as insulation to minimize dissipation of the electrical signal as it travels down the axon. Myelin’s presence on the axon greatly increases the speed of conduction of the electrical signal, because the fat prevents any electricity from “leaking out”. This insulation is important, as the axon from a human motor neuron can be as long as a meter—from the base of the spine to the toes. Periodic gaps in the myelin sheath are called nodes of Ranvier. At these nodes, the signal is “recharged” as it travels along the axon. Glial Cells The myelin sheath is not actually part of the neuron. Myelin is produced by glial cells (or simply glia, or “glue” in Greek), which are non-neuronal cells that provide support for the nervous system. Glia function to hold neurons in place (hence their Greek name), supply them with nutrients, provide insulation, and remove pathogens and dead neurons. In the central nervous system, the glial cells that form the myelin sheath are called oligodendrocytes; in the peripheral nervous
  • 16. system, they are called Schwann cells. Neuron in the central nervous system: This neuron diagram also shows the oligodendrocyte, myelin sheath, and nodes of Ranvier. Types of Neurons There are three major types of neurons: sensory neurons, motor neurons, and interneurons. All three have different functions, but the brain needs all of them to communicate effectively with the rest of the body (and vice versa). Sensory Neurons Sensory neurons are neurons responsible for converting external stimuli from the environment into corresponding internal stimuli. They are activated by sensory input, and send projections to other elements of the nervous system, ultimately conveying sensory information to the brain or spinal cord. Unlike the motor neurons of the central nervous system (CNS), whose inputs come from other neurons, sensory neurons are activated by physical stimuli (such as visible light, sound, heat, physical contact, etc.) or by chemical signals (such as smell and taste). Most sensory neurons are pseudounipolar, meaning they have an axon that branches into two extensions—one connected to dendrites that receive sensory information and another that transmits this information to the spinal cord. Motor Neurons Motor neurons are neurons located in the central nervous system, and they project their axons outside of the CNS to directly or indirectly control muscles. The interface between a motor neuron and muscle fiber is a specialized synapse called the neuromuscular junction. The structure of motor neurons is multipolar, meaning each cell contains a single axon and multiple dendrites. This is the most common type of neuron. Interneurons Interneurons are neither sensory nor motor; rather, they act as
  • 17. the “middle men” that form connections between the other two types. Located in the CNS, they operate locally, meaning their axons connect only with nearby sensory or motor neurons. Interneurons can save time and therefore prevent injury by sending messages to the spinal cord and back instead of all the way to the brain. Like motor neurons, they are multipolar in structure. Stages of the Action Potential Neural impulses occur when a stimulus depolarizes a cell membrane, prompting an action potential which sends an “all or nothing” signal. Key Points: · The neurons (or excitable nerve cells) of the nervous system conduct electrical impulses, or signals, that serve as communication between sensory receptors, muscles and glands, and the brain and spinal cord. · An action potential occurs when an electrical signal disrupts the original balance of Na+ and K+ within a cell membrane, briefly depolarizing the concentrations of each. · An electrical impulse travels along the axon via depolarized voltage-gated ion channels in the membrane, and can either “jump” along a myelinated area or travel continuously along an unmyelinated area. · While an action potential is being generated by a cell, no other action potential may be generated until the cell’s channels return to their resting state. · Action potentials generated by neural impulses are “all or nothing,” meaning the signal reaches the threshold for communication or it doesn’t. No signal is stronger or weaker than another. Key Terms: · polarity: The spatial differences in the shape, structure, and function of cells. Almost all cell types exhibit some sort of polarity, which enables them to carry out specialized functions. · action potential: A short-term change in the electrical
  • 18. potential that travels along a cell, such as a nerve or muscle fiber, and allows nerves to communicate. · neural impulse: The signal transmitted along a nerve fiber, either in response to a stimulus (such as touch, pain, or heat), or as an instruction from the brain (such as causing a muscle to contract). · resting potential: The nearly latent membrane potential of inactive cells. Neural Impulses in the Nervous System The central nervous system (CNS) goes through a three-step process when it functions: sensory input, neural processing, and motor output. The sensory input stage is when the neurons (or excitable nerve cells) of the sensory organs are excited electrically. Neural impulses from sensory receptors are sent to the brain and spinal cord for processing. After the brain has processed the information, neural impulses are then conducted from the brain and spinal cord to muscles and glands, which is the resulting motor output. A neuron affects other neurons by releasing a neurotransmitter that binds to chemical receptors. The effect upon the postsynaptic (receiving) neuron is determined not by the presynaptic (sending) neuron or by the neurotransmitter itself, but by the type of receptor that is activated. A neurotransmitter can be thought of as a key, and a receptor as a lock: the key unlocks a certain response in the postsynaptic neuron, communicating a particular signal. However, in order for a presynaptic neuron to release a neurotransmitter to the next neuron in the chain, it must go through a series of changes in electric potential. Stages of Neural Impulses “Resting potential ” is the name for the electrical state when a neuron is not actively being signaled. A neuron at resting potential has a membrane with established amounts of sodium (Na+) and potassium (K+) ions on either side, leaving the inside of the neuron negatively charged relative to the outside. The action potential is a rapid change in polarity that moves
  • 19. along the nerve fiber from neuron to neuron. In order for a neuron to move from resting potential to action potential—a short-term electrical change that allows an electrical signal to be passed from one neuron to another—the neuron must be stimulated by pressure, electricity, chemicals, or another form of stimuli. The level of stimulation that a neuron must receive to reach action potential is known as the threshold of excitation, and until it reaches that threshold, nothing will happen. Different neurons are sensitive to different stimuli, although most can register pain. The action potential has several stages. 1. Depolarization: A stimulus starts the depolarization of the membrane. Depolarization is caused when positively charged sodium ions rush into a nerve cell. As these positive ions rush in, the membrane of the stimulated cell reverses its polarity so that the outside of the membrane is negative relative to the inside. 2. Repolarization. Once the electric gradient has reached the threshold of excitement, the “downswing” of repolarization begins. The channels that let the positive sodium ion channels through close up, while channels that allow positive potassium ions open, resulting in the release of positively charged potassium ions from the neuron. This expulsion acts to restore the localized negative membrane potential of the cell, bringing it back to its normal voltage. 3. Refractory Phase. The refractory phase takes place over a short period of time after the depolarization stage. Shortly after the sodium gates open, they close and go into an inactive conformation. The sodium gates cannot be opened again until the membrane is repolarized to its normal resting potential. A sodium-potassium pump returns sodium ions to the outside and potassium ions to the inside. During the refractory phase this particular area of the nerve cell membrane cannot be depolarized. Therefore, the neuron cannot reach action potential during this “rest period.”
  • 20. Action potentials: A neuron must reach a certain threshold in order to begin the depolarization step of reaching the action potential. This process of depolarization, repolarization, and recovery moves along a nerve fiber from neuron to neuron like a very fast wave. While an action potential is in progress, another cannot be generated under the same conditions. In unmyelinated axons (axons that are not covered by a myelin sheath), this happens in a continuous fashion because there are voltage-gated channels throughout the membrane. In myelinated axons (axons covered by a myelin sheath), this process is described as saltatory because voltage-gated channels are only found at the nodes of Ranvier, and the electrical events seem to “jump” from one node to the next. Saltatory conduction is faster than continuous conduction. The diameter of the axon also makes a difference, as ions diffusing within the cell have less resistance in a wider space. Damage to the myelin sheath from disease can cause severe impairment of nerve-cell function. In addition, some poisons and drugs interfere with nerve impulses by blocking sodium channels in nerves. More on this point in the next Lecture. All-or-none Signals The amplitude of an action potential is independent of the amount of current that produced it. In other words, larger currents do not create larger action potentials. Therefore, action potentials are said to be all-or-none signals, since either they occur fully or they do not occur at all. The frequency of action potentials is correlated with the intensity of a stimulus. This is in contrast to receptor potentials, whose amplitudes are dependent on the intensity of a stimulus. Reuptake Reuptake refers to the reabsorption of a neurotransmitter by a presynaptic (sending) neuron after it has performed its function of transmitting a neural impulse. Reuptake is necessary for normal synaptic physiology because it allows for the recycling
  • 21. of neurotransmitters and regulates the neurotransmitter level in the synapse, thereby controlling how long a signal resulting from neurotransmitter release lasts. Mechanics of the Action Potential The synapse is the site at which a chemical or electrical exchange occurs between the presynaptic and postsynaptic cells. Key Points: · Receptors are pores that admit chemical or electrical signals into the postsynaptic cell. There are two main types of receptor: ligand-gated ion channels, which receive neurostransmitters, and g-protein coupled receptors, which do not. · There are two types of possible reactions at the synapse: a chemical reaction or an electrical reaction. · During a chemical reaction, neurotransmitters trigger the opening of ligand-gated ion channels on the membrane of the postsynaptic cell, resulting in a modification of the cell’s interior chemical composition and, in some cases, physical structure. · In an electrical reaction, the electrical charge of one cell is influenced by another. · Although electrical synapses yield faster reactions, chemical synapses result in stronger, more complex changes to the postsynaptic cell. Key Terms: · vesicle: A membrane-bound compartment found in a cell. · action potential: A short-term change in the electrical potential that travels along a cell, such as a nerve or muscle fiber, and allows nerves to communicate. · depolarization: The act of depriving of polarity, or the result of such action; reduction to an unpolarized condition. · membrane potential: The voltage across the cell membrane, with the inside relative to the outside. Synapses The synapse is the junction where neurons trade information. It is not a physical component of a cell but rather a name for the gap between two cells: the presynaptic cell (giving the signal)
  • 22. and the postsynaptic cell (receiving the signal). There are two types of possible reactions at the synapse—chemical or electrical. During a chemical reaction, a chemical called a neurotransmitter is released from one cell into another. In an electrical reaction, the electrical charge of one cell is influenced by the charge an adjacent cell. The electrical response of a neuron to multiple synaptic inputs: Synaptic responses summate in order to bring the postsynaptic neuron to the threshold of excitation, so it can fire an action potential (represented by the peak on the chart). All synapses have a few characteristics in common: · Presynaptic cell: a specialized area within the axon of the giving cell that transmits information to the dendrite of the receiving cell. · Synaptic cleft: the small space at the synapse that receives neurotransmitters. · G-protein coupled receptors: receptors that sense molecules outside the cell and thereby activate signals within it. · Ligand-gated ion channels: receptors that are opened or closed in response to the binding of a chemical messenger. · Postsynaptic cell: a specialized area within the dendrite of the receiving cell that contains receptors designed to process neurotransmitters. The Electrical Synapse The stages of an electrical reaction at a synapse are as follows: 1. Resting potential. The membrane of a neuron is normally at rest with established concentrations of sodium ions (Na+) and potassium ions (K+) on either side. The membrane potential (or, voltage across the membrane) at this state is -70 mV, with the inside being negative relative to the outside. 2. Depolarization. A stimulus begins the depolarization of the membrane. Depolarization, also referred to as the “upswing,” occurs when positively charged sodium ions (Na+) suddenly rush through open sodium gates into a nerve cell. If the membrane potential reaches -55 mV, it has reached the
  • 23. threshold of excitation. Additional sodium rushes in, and the membrane of the stimulated cell actually reverses its polarity so that the outside of the membrane is negative relative to the inside. The change in voltage stimulates the opening of additional sodium channels (called a voltage-gated ion channel), providing what is known as a positive feedbackloop. Eventually, the cell potential reaches +40 mV, or the action potential. 3. Repolarization. The “downswing” of repolarization is caused by the closing of sodium ion channels and the opening of potassium ion channels, resulting in the release of positively charged potassium ions (K+) from the nerve cell. This expulsion acts to restore the localized negative membrane potential of the cell. 4. Refractory Phase. The refractory phase is a short period of time after the repolarization stage. Shortly after the sodium gates open, they close and go into an inactive conformation where the cell’s membrane potential is actually even lower than its baseline -70 mV. The sodium gates cannot be opened again until the membrane has completely repolarized to its normal resting potential, -70 mV. The sodium-potassium pump returns sodium ions to the outside and potassium ions to the inside. During the refractory phase this particular area of the nerve cell membrane cannot be depolarized; the cell cannot be excited. The Chemical Synapse The process of a chemical reaction at the synapse has some important differences from an electrical reaction. Chemical synapses are much more complex than electrical synapses, which makes them slower, but also allows them to generate different results. Like electrical reactions, chemical reactions involve electrical modifications at the postsynaptic membrane, but chemical reactions also require chemical messengers, such as neurotransmitters, to operate. Neuron & chemical synapse: This image shows electric impulses traveling between neurons; the inset shows a chemical reaction occurring at the synapse.
  • 24. A basic chemical reaction at the synapse undergoes a few additional steps: 1. The action potential (which occurs as described above) travels along the membrane of the presynaptic cell until it reaches the synapse. The electrical depolarization of the membrane at the synapse causes channels to open that are selectively permeable, meaning they specifically only allow the entry of positive sodium ions (Na+). 2. The ions flow through the presynaptic membrane, rapidly increasing their concentration in the interior. 3. The high concentration activates a set of ion-sensitive proteins attached to vesicles, which are small membrane compartments that contain a neurotransmitter chemical. 4. These proteins change shape, causing the membranes of some “docked” vesicles to fuse with the membrane of the presynaptic cell. This opens the vesicles, which releases their neurotransmitter contents into the synaptic cleft, the narrow space between the membranes of the pre- and postsynaptic cells. 5. The neurotransmitter diffuses within the cleft. Some of it escapes, but the rest of it binds to chemical receptor molecules located on the membrane of the postsynaptic cell. 6. The binding of neurotransmitter causes the receptor molecule to be activated in some way. Several types of activation are possible, depending on what kind of neurotransmitter was released. In any case, this is the key step by which the synaptic process affects the behavior of the postsynaptic cell. 7. Due to thermal shaking, neurotransmitter molecules eventually break loose from the receptors and drift away. 8. The neurotransmitter is either reabsorbed by the presynaptic cell and repackaged for future release, or else it is broken down metabolically. Differences Between Electrical and Chemical Synapses · Electrical synapses are faster than chemical synapses because the receptors do not need to recognize chemical messengers. The synaptic delay for a chemical synapse is typically about 2 milliseconds, while the synaptic delay for an electrical synapse
  • 25. may be about 0.2 milliseconds. · Because electrical synapses do not involve neurotransmitters, electrical neurotransmission is less modifiable than chemical neurotransmission. · The response is always the same sign as the source. For example, depolarization of the presynaptic membrane will always induce a depolarization in the postsynaptic membrane, and vice versa for hyperpolarization. · The response in the postsynaptic neuron is generally smaller in amplitude than the source. The amount of attenuation of the signal is due to the membrane resistance of the presynaptic and postsynaptic neurons. · Long-term changes can be seen in electrical synapses. For example, changes in electrical synapses in the retina of your eyeare seen during light and dark adaptations of the retina. Neurotransmitters Neurotransmitters are chemicals that transmit signals from a neuron across a synapse to a target cell. Key Points: · Neurotransmitters dictate communication between cells by binding to specific receptors and depolarizing or hyperpolarizing the cell. · Inhibitory neurotransmitters cause hyperpolarization of the postsynaptic cell; excitatory neurotransmitters cause depolarization of the postsynaptic cell. · Too little of a neurotransmitter may cause the over accumulation of proteins, leading to disorders like Alzheimer’s disease. Too much of a neurotransmitter may block receptors required for proper brain function, leading to disorders like schizophrenia. · The three neurotransmitter systems in the brain are
  • 26. cholinergic, amino acids, and biogenic amines. Key Terms · reuptake: The reabsorption of a neurotransmitter by a neuron after the transmission of a neural impulse across a synapse. · vesicle: A membrane-bound compartment found in a cell. · action potential: A short-term change in the electrical potential that travels along a cell (such as a nerve or muscle fiber); the basis of neural communication. Neurotransmitters are chemicals that transmit signals from a neuron to a target cell across a synapse. When called upon to deliver messages, they are released from their synaptic vesicles on the presynaptic (giving) side of the synapse, diffuse across the synaptic cleft, and bind to receptors in the membrane on the postsynaptic (receiving) side. An action potential is necessary for neurotransmitters to be released, which means that neurons must reach a certain threshold of electric stimulation in order to complete the reaction. A neuron has a negative charge inside the cell membrane relative to the outside of the cell membrane; when stimulation occurs and the neuron reaches the threshold of excitement this polarity is reversed. This allows the signal to pass through the neuron. When the chemical message reaches the axon terminal, channels in the postsynaptic cell membrane open up to receive neurotransmitters from vesicles in the presynaptic cell. Inhibitory neurotransmitters cause hyperpolarization of the postsynaptic cell (that is, decreasing the voltage gradient of the cell, thus bringing it further away from an action potential), while excitatory neurotransmitters cause depolarization (bringing it closer to an action potential). Neurotransmitters match up with receptors like a key in a lock. A neurotransmitter binds to its receptor and will not bind to receptors for other neurotransmitters, making the binding a specific chemical event. There are several systems of neurotransmitters found at various synapses in the nervous system. The following groups refer to
  • 27. the specific chemicals, and within the groups are specific systems, some of which block other chemicals from entering the cell and some of which permit the entrance of chemicals that were blocked before. Cholinergic System The cholinergic system is a neurotransmitter system of its own, and is based on the neurotransmitter acetylcholine (ACh). This system is found in the autonomic nervous system, as well as distributed throughout the brain. The cholinergic system has two types of receptors: the nicotinic receptor and the acetylcholine receptor, which is known as the muscarinic receptor. Both of these receptors are named for chemicals that interact with the receptor in addition to the neurotransmitter acetylcholine. Nicotine, the chemical in tobacco, binds to the nicotinic receptor and activates it similarly to acetylcholine. Muscarine, a chemical product of certain mushrooms, binds to the muscarinic receptor. However, they can not bind to each others’ receptors. Amino Acids Another group of neurotransmitters are amino acids, including glutamate (Glu), GABA (gamma-aminobutyric acid, a derivative of glutamate), and glycine (Gly). These amino acids have an amino group and a carboxyl group in their chemical structures. Glutamate is one of the 20 amino acids used to make proteins. See Lecture 6. Each amino acid neurotransmitter is its own system, namely the glutamatergic, GABAergic, and glycinergic systems. They each have their own receptors and do not interact with each other. Amino acid neurotransmitters are eliminated from the synapse by reuptake. A pump in the cell membrane of the presynaptic element, or sometimes a neighboring glial cell, clears the amino acid from the synaptic cleft so that it can be recycled, repackaged in vesicles, and released again. The reuptake process: This illustration shows the process of
  • 28. reuptake, in which leftover neurotransmitters are returned to vesicles in the presynaptic cell. Biogenic Amines Another class of neurotransmitter is the biogenic amine, a group of neurotransmitters made enzymatically from amino acids. They have amino groups in them, but do not have carboxyl groups and are therefore no longer classified as amino acids. Neuropeptides A neuropeptide is a neurotransmitter molecule made up of chains of amino acids connected by peptide bonds, similar to proteins. However, proteins are long molecules while some neuropeptides are quite short. Neuropeptides are often released at synapses in combination with another neurotransmitter. Dopamine Dopamine is the best-known neurotransmitter of the catecholamine group. The brain includes several distinct dopamine systems, one of which plays a major role in reward- motivated behavior. Most types of reward increase the level of dopamine in the brain, and a variety of addictive drugs increase dopamine neuronal activity. Other brain dopamine systems are involved in motor control and in controlling the release of several other important hormones ( a regulatory substance produced in an organismand transported in tissue fluids such as blood or sap to stimulate specific cells or tissues into action ). More on this in the next Lecture. Effect on the Synapse The effect of a neurotransmitter on the postsynaptic element is entirely dependent on the receptor protein. If there is no receptor protein in the membrane of the postsynaptic element, then the neurotransmitter has no effect. The depolarizing (more likely to reach an action potential) or hyperpolarizing (less likely to reach an action potential) effect is also dependent on the receptor. When acetylcholine binds to the nicotinic receptor, the postsynaptic cell is depolarized. However, when acetylcholine binds to the muscarinic receptor, it might cause
  • 29. depolarization or hyperpolarization of the target cell. The amino acid neurotransmitters (glutamate, glycine, and GABA) are almost exclusively associated with just one effect. Glutamate is considered an excitatory amino acid because Glu receptors in the adult cause depolarization of the postsynaptic cell. Glycine and GABA are considered inhibitory amino acids, again because their receptors cause hyperpolarization, making the receiving cell less likely to reach an action potential. The Right Dose Sometimes too little or too much of a neurotransmitter may affect an organism’s behavior or health. The underlying cause of some neurodegenerative diseases, such as Parkinson’s disease, appears to be related to over accumulation of proteins, which under normal circumstances would be regulated by the presence of dopamine. On the other hand, when an excess of the neurotransmitter dopamine blocks glutamate receptors, disorders like Schizophrenia can occur. Neural Networks Neural networks consist of a series of interconnected neurons, and serve as the interface for neurons to communicate with each other. Key Points: · The connections between neurons form a highly complex network through which signals or impulses are communicated across the body. · The basic kinds of connections between neurons are chemical synapses and electrical gap junctions, through which either chemical or electrical impulses are communicated between neurons. · Neural networks are primarily made up of axons, which in some cases deliver information as far as two meters. · Networks formed by interconnected groups of neurons are capable of a wide variety of functions. In fact the range of capabilities possible for even small groups of neurons are beyond our current understanding. · Modern science views the function of the nervous system both
  • 30. in terms of stimulus -response chains and in terms of intrinsically generated activity patterns within neurons. · Cell assembly, or Hebbian theory, asserts that “cells that fire together wire together,” meaning neural networks can be created through associative experience and learning. Key Terms: · cell assembly: Also referred to as Hebbian theory; the concept that “cells that fire together wire together,” meaning neural networks can be created through associative experience and learning. · action potential: A short-term change in the electrical potential that travels along a cell such as a nerve or muscle fiber, and allows nerves to communicate. · plasticity: The ability to change and adapt over time. A neural network (or neural pathway) is the interface through which neurons communicate with one another. These networks consist of a series of interconnected neurons whose activation sends a signal or impulse across the body. Neural networks: A neural network (or neural pathway) is the complex interface through which neurons communicate with one another. See top of Lecture. Perhaps now you can begin to appreciate the path breaking research of Ramón y Cajal. As a child he was transferred many times from one school to another because of behavior that was declared poor, rebellious, and showing an “anti-authoritarian attitude.” An extreme example of his precociousness and rebelliousness at the age of eleven is his 1863 imprisonment for destroying his neighbor's yard gate with a homemade cannon. He and Camillo Golgi received the Nobel Prize in Physiology or Medicine in 1906. Ramón y Cajal was the first person of
  • 31. Spanish origin to win a Nobel Prize. SUMMARY of LECTURE 9 The connections between neurons form a highly complex network. The basic kinds of connections between neurons are chemical synapses and electrical gap junctions, through which either chemical or electrical impulses are communicated between neurons. The method through which neurons interact with neighboring neurons usually consists of several axon terminals connecting through synapses to the dendrites on other neurons. If a stimulus creates a strong enough input signal in a nerve cell, the neuron sends an action potential and transmits this signal along its axon. The axon of a nerve cell is responsible for transmitting information over a relatively long distance, and so most neural pathways are made up of axons. Some axons are encased in a lipid-coated myelin sheath, making them appear a bright white; others that lack myelin sheaths (i.e., are unmyelinated) appear a darker beige color, which is generally called gray. The process of synaptic transmission in neurons: Neurons interact with other neurons by sending a signal, or impulse, along their axon and across a synapse to the dendrites of a neighboring neuron. Some neurons are responsible for conveying information over long distances. For example, motor neurons, which travel from the spinal cord to the muscle, can have axons up to a meter in length in humans. The longest axon in the human body is almost two meters long in tall individuals and runs from the big toe to the medulla oblongata of the brain stem. The Capacity of Neural Networks The basic neuronal function of sending signals to other cells
  • 32. includes the capability for neurons to exchange signals with each other. Networks formed by interconnected groups of neurons are capable of a wide variety of functions, including feature detection, pattern generation, and timing. In fact, it is difficult to assign limits to the types of information processing that can be carried out by neural networks. Given that individual neurons can generate complex temporal patterns of activity independently, the range of capabilities possible for even small groups of neurons are beyond current understanding. However, we do know that we have neural networks to thank for much of our higher cognitive functioning. Behaviorist Approach Historically, the predominant view of the function of the nervous system was as a stimulus-response associator. In this conception, neural processing begins with stimuli that activate sensory neurons, producing signals that propagate through chains of connections in the spinal cord and brain, giving rise eventually to activation of motor neurons and thereby to muscle contraction or other overt responses. Charles Sherrington, in his influential 1906 book The Integrative Action of the Nervous System, developed the concept of stimulus-response mechanisms in much more detail, and behaviorism, the school of thought that dominated psychology through the middle of the 20th century, attempted to explain every aspect of human behavior in stimulus-response terms. Hybrid Approach Experimental studies of electrophysiology, beginning in the early 20th century and reaching high productivity by the 1940s, showed that the nervous system contains many mechanisms for generating patterns of activity intrinsically—without requiring an external stimulus. Neurons were found to be capable of producing regular sequences of action potentials (“firing”) even in complete isolation. When intrinsically active neurons are connected to each other in complex circuits, the possibilities for generating intricate temporal patterns become far more extensive. A modern conception views the function of the
  • 33. nervous system partly in terms of stimulus-response chains, and partly in terms of intrinsically generated activity patterns; both types of activity interact with each other to generate the full repertoire of behavior. Hebbian Theory In 1949, neuroscientist Donald Hebb proposed that simultaneous activation of cells leads to pronounced increase in synaptic strength between those cells, a theory that is widely accepted today. Cell assembly, or Hebbian theory, asserts that “cells that fire together wire together,” meaning neural networks can be created through associative experience and learning. Since Hebb’s discovery, neuroscientists have continued to find evidence of plasticity and modification within neural networks. CHE 102: LECTURE 7 FOSSIL FUELS An oil refinery or petroleum refinery is an industrial plant where crude oil is transformed and refined into more useful products such as gasoline, diesel fuel, jet fuel, naptha, asphalt, heating oil, kerosene, liquefied petroleum gas, and fuel oils. Oil, coal, natural gas and other fossil fuels are called "fossil" because these fuels are the preserved carbon-hydrogen remnants of ancient life. Coal is formed from plants that decomposed and accumulated in ancient swamps. EXAMPLES: Fossil Fuels: Coal: Coal is the primary fuel for the production of electricity and is responsible for about 40% of the electric power supply in the United States.
  • 34. Oil: Oil is the primary source for the world's transportation. Natural Gas: About 27% of U.S. energy is fueled by natural gas. Natural gas is the cleanest burning fossil fuel. CHEMISTRY: fossil fuel combustion. One molecule of methane, combined with two oxygen molecules, react to form a carbon dioxide molecule, and two water molecules (usually given off as steam or water vapor) releasing energy. See Lecture 3 and figure below. COAL Coal is a combustible black or brownish-black sedimentary rock usually occurring in rock strata in layers or veins called coal beds or coal seams. The harder forms, such as anthracite coal, can be regarded as metamorphic rock because of later exposure to elevated temperature and pressure. NOTE: Geologists classify rocks into three main rock types. Rocks are either a single mineral or a combinations of minerals. Sedimentary rocks are a type of rock that formed by the accumulation or deposition of small particles (minerals or organic matter) at the Earth’s surface, subsequently followed by their cementation on the floor of oceans or other bodies of water. Examples: sandstone, limestone (see below). Limestone is a carbonate sedimentary rock that is often composed of the skeletal fragments of marine organisms such as coral, foraminifera, and molluscs. Its major materials are the minerals calcite (CaCO3).
  • 35. and aragonite, which are different crystal forms of calcium carbonate (CaCO3). Metamorphic rocks arise from the transformation of existing rock types, in a process called metamorphism, which means "change in form". The original rock is subjected to heat and pressure, causing profound physical or chemical changes. The precursor may be a sedimentary, igneous, or existing metamorphic rock. Examples: slate, marble. Marble is a metamorphic rock composed of recrystallized carbonate minerals, most commonly calcite (see above) or dolomite. In Geology, the term marble refers to metamorphosed limestone. The Taj Mahal in the Indian city of Agra is entirely clad in marble.I was amazed to find that the limestone in the Taj Mahal structure is so transparent, the interior of this architectural masterpiece is “illuminated.” Igneous rock is formed through the cooling and solidification of lava (or magma) from volcanic eruptions. The magma can be derived from partial melts of existing rocks in either a planet's mantle or crust. Example: obsidian, granite (see below). The word "granite" comes from the Latin granum, a grain, in reference to the coarse-grained structure of such a rock. Strictly speaking, granite is an igneous rock with between 20% and 60% quartz (See Lecture 4) by volume, and at least 35% of the total, by feldspar [ Feldspar is an abundant rock-forming mineral
  • 36. typically occurring as colorless or pale-colored crystals and consisting of aluminum silicates of potassium, sodium, and calcium] . A crystal of one form of feldspar shown below. Coal is composed primarily of carbon, along with variable quantities of other elements, chiefly hydrogen, sulfur, oxygen, and nitrogen. Coal is a fossil fuel that forms when dead plant matter is converted into peat, which in turn is converted into lignite, then sub-bituminous coal, after that bituminous coal, and lastly anthracite. Thus both biological and geological processes are involved in its formation. The geological processes take place over millions of years. There are six main types of coal that are regularly used in power plants or by other sectors of society: Peat. Peat is formed from decaying vegetation, and is considered to be the precursor of coal Lignite. Lignite is formed from compressed peat, and is often referred to as brown coal Bituminous/Sub Bituminous Coal Steam Coal Anthracite Graphite Coal Sedimentary rock
  • 37. Anthracite coal Element Composition of Various types of Coal: Mass % of each element. type of coal C H O N S lignite 71 4 23 1 1 subbituminous 77 5 16 1 1 bituminous 80 6 8 1 5 anthracite 92 3 3 1 1 NOTE: Anthracite is the “cleanest” coal, lignite the “dirtiest.” Sources of Energy: fossil fuels (2007). petroleum 36.0 % coal 27.4 % natural gas 23.0% The following two account for 14.8%. nuclear 8.5 % hydroelectric 6.3 % All of the following account for 0.9%. geothermal solar tidal
  • 38. wood waste Historical record of fossil fuel use: Wood Coal Petroleum/Natural Gas Hydro/Nuclear 1850 91% 9% 1900 21% 71% 5% 3% 1950 6% 36% 52% 6% 1975 3% 18% 73% 6% 2000 4% 23% 62% 11% The separation of petroleum into “fractions” (by length of carbon chain) is what occurs in oil refineries. C5 – C10 gasoline C10 – C18 kerosene C15 – C25 diesel fuel, heating oil, lubricating oil > C25 asphalt In the New York Times today (4/21/2020), the banner headline is: “Coronavirus Live Updates: Trump Says He Will Halt Immigration; Oil Prices Crater, and Stocks Fall”
  • 39. The oil market meltdown is continuing. Brent crude, the international benchmark, was down about 18 percent, to $20.90 a barrel. GREENHOUSE EFFECT: Overview 1. Solar radiation reaches the Earth's atmosphere - some of this is reflected back into space. 2. The rest of the sun's energy is absorbed by the land and the oceans, heating the Earth. 3. Heat radiates from Earth towards space. 4. Some of this heat is trapped by greenhouse gases in the atmosphere, keeping the Earth warm enough to sustain life. A greenhouse gas is a gas that absorbs and emits radiant energy within the (thermal) infrared range. Greenhouse gases cause the greenhouse effect on planets. Greenhouse gases include water vapor, carbon dioxide, methane, nitrous oxide, ozone and some artificial chemicals such as chlorofluorocarbons (CFCs). The molecular structures of ozone and nitrous oxide are shown below. OZONE
  • 40. NOTE: The ozone layer or ozone shield is a region of Earth's stratosphere that absorbs most of the Sun's ultraviolet radiation. The ozone layer contains a high concentration of ozone in relation to other gases in the layer, although still small in relation to gases (e.g. oxygen O2 and nitrogen N2 ) in other regions of the stratosphere. NITROUS OXIDE (“laughing gas”) NOTE: Nitrous oxide has significant medical uses, especially in surgery and dentistry, for its anaesthetic and pain reducing effects. Its colloquial name "laughing gas", coined by Humphry Davy (see Lecture 4 ), is due to the euphoric effects upon inhaling it, a property that has led to its recreational use as a dissociative anaesthetic ( A unique anesthesia characterized by analgesia and amnesia with minimal effect on respiratory function. The patient does not appear to be anesthetized and can swallow and open eyes but does not process information). It is also used as an oxidizer in rocket propellants and in motor racing to increase the power output of engines. 5. Human activities such as burning fossil fuels, agriculture and land clearing are increasing the amount of greenhouse gases released into the atmosphere. 6. This results in trapping extra heat, and causing the Earth's temperature to rise.
  • 41. The greenhouse effect is a natural process that warms the Earth’s surface. Absorbed thermal energy warms the atmosphere and the surface of the Earth. This process maintains the Earth’s temperature at around 91.4 degrees Fahrenheit warmer than it would otherwise be, allowing life on Earth to exist. The problem we now face is that human activities – particularly burning fossil fuels (coal, oil and natural gas), agriculture and land clearing – are increasing the concentrations of greenhouse gases. This is the enhanced greenhouse effect, which is contributing to global warming, an overall increase in the temperature of the Ear Average global temperatures from 2010 to 2019 compared to a baseline average from 1951 to 1978. Source: NASA. CARBON FOOTPRINT A carbon footprint is historically defined as the total greenhouse gas (GHG) emissions caused by an individual, event, organization, or product, expressed as carbon dioxide equivalent. Greenhouse gases, including the carbon-containing gases carbon dioxide and methane, can be emitted through the burning of fossil fuels, land clearance (e.g. in the Amazon basin) and the production and consumption of food, manufactured goods, materials, wood, roads, buildings, transportation and other services. In most cases, the total carbon footprint cannot be calculated exactly because of inadequate knowledge of and data about the complex interactions between contributing processes, including the influence of natural processes that store or release carbon dioxide. For this reason, the following definition of a carbon footprint has been proposed: Carbon Footprint: A measure of the total amount of carbon
  • 42. dioxide (CO2) and methane (CH4) emissions of a defined population, system or activity, considering all relevant sources, sinks and storage within the spatial and temporal boundary of the population, system or activity of interest. Most of the carbon footprint emissions for the average U.S. household come from "indirect" sources, e.g. fuel burned to produce goods far away from the final consumer. These are distinguished from emissions which come from burning fuel directly in one's car or stove, commonly referred to as "direct" sources of the consumer's carbon footprint. The 100-year global warming potential (GWP100) is calculated with reference to carbon dioxide. Coal - Wikipedia https://en.wikipedia.org/wiki/Coal GLOBAL WARMING Global warming - Wikipedia en.wikipedia.org › wiki › Global_warming ECONOMIC IMPLICATIONS The Economic Impact of Greenhouse Gas Emissions | Clive Best clivebest.com/?p=7139
  • 43. LECTURE 9. From Alcohol and Aspirin to Hallucinogens and Opioids La Nuit Etoilée (The Starry Night) is an oil on canvas by Dutch post-impressionist painter Vincent van Gogh (1853-1890). Painted in June 1889, it describes the view from the east-facing window of his asylum room at Saint-Rémy-de-Provence, just before sunrise, with the addition of an ideal village. He spent a long period in 1889-90 in a clinic because of his mental instability, before committing suicide. You do not have to be a chemist to wonder about the source of the swirls, spirals and other strange effects. Van Gogh's instability and suicide have been blamed on the liqueur-like drink absinthe, a fashionable French beverage in the half century up to the first world war. Absinthe, is a green liquid with an anise smell, made by distilling a mixture of alcohol, herbs (notably wormwood) and water. In the late 19th century, it became a national drink in France. Fashionable among the artistic community, it became cheap enough to be the spirit “beverage of choice” among the poor. Writers such as Baudelaire, Edgar Allan Poe and Verlaine relied upon it, and a whole range of artists (Degas, Gauguin, Manet, Picasso, Toulouse-Lautrec, and Van Gogh) are associated with it, often for including it in their paintings. Known as la fée verte (the green fairy), absinthe gave rise to l'heure verte, the time (5 pm) when drinkers in all walks of life went to a café for their absinthe, what we would now call a “Happy Hour”. L'Absinthe Artist Edgar Degas Year
  • 44. 1875–76 We begin by considering alcoholic beverages and their effect on the brain. How does alcohol affect the brain? Alcohol has a profound effect on the complex structures of the brain. It blocks chemical signals between brain cells (neurons), leading to the common intermediate symptoms of intoxication, including impulsive behavior, slurred speech, poor memory, and slowed reflexes. If heavy drinking continues over extended periods of time, the brain adopts to the blocked signals by responding more dramatically to certain brain chemicals, the neurotransmitters. After alcohol leaves the system, the brain continues over- activating the neurotransmitters, causing painful and potentially dangerous withdrawal symptoms that can damage brain cells. This damage is made more acute by “binge drinking” and sudden withdrawal. Alcohols damage to the brain can take several forms. The first is neurotoxicity, which occurs when neurons over react to neurotransmitters for too long. Too much exposure to a neurotransmitter can cause neurons to eventually “burn out.” Since neurons make up the pathways between different parts of the brain, when they begin “burning out,” it can cause
  • 45. noticeable slowing in the response of these pathways. People with alcohol dependence often experience “brain shrinkage,” which is reduced volume of both gray matter (cell bodies) and white matter (cell pathways) over time. There are some subtle differences in how brain damage occurs in men and women, but regardless of gender, loss of brain matter increases with age and amount of alcohol consumed. What are the observable effects of this damage? Since alcohol affects a large portion of the brain, many different kinds of cognitive impairment can occur as a result of heavy drinking, including problems with verbal fluency and verbal learning, processing speed, working memory, attention, problem solving, spatial processing and impulsivity. Parts of the brain relating to memory and “higher functions” ( for example, problem solving and impulse control) are more susceptible to damage than other parts of the brain, so problems in these areas tend to be worse than others. Adolescents are especially at risk for long-lasting or permanent damage and performance deficits, since their most-impacted areas of the brain are still in development. Without treatment, cognitive impairment grows worse, eventually developing into a lasting syndrome known as alcohol related dementia. This syndrome represents about 10% of all dementia cases (additionally, alcohol is estimated to contribute to roughly 29% of all other dementia cases). Cognitive deficits are made worse by malnutrition, especially a
  • 46. deficiency of vitamin B (a common deficiency in alcohol- dependent individuals). Malnutrition and heavy alcohol consumption can cause serious impairments in memory and language over time and can potentially result in permanent cognitive disorder called Wernicke-Korsakoff syndrome, which causes amnesia and can lead to coma if left untreated. In Lecture 5, we commented on the different physiological effects induced by methanol and ethanol. methanol and ethanolMethanol is a highly toxic alcohol with a smell and taste similar to ethanol. Small amounts (around 50 - 100 ml ) cause permanent blindness and severe neurological dysfunction leading to death. More than half of methanol-related morbidity and mortality is classified as accidental and therefore preventable. In addition, it can be suicidal by ingestion of a variety of commercial paint thinners, gasoline anti-freeze, windshield products, organic solvents, shellac varnish, washer fluid, photocopying fluids, perfumes, and in some eau de cologne. Occasionally, it is due to the fraudulent adulteration of wine or other alcoholic beverages. Its ingestion causes high anion gap metabolic acidosis from the production of formic and lactic acids and central nervous system disturbances ranging from inebriation and drowsiness to obtundation (A condition in which the senses have been dulled by trauma, mistreatment, or psychological stress.), seizure and coma. Aspirin
  • 47. The active ingredient in aspirin is acetylsalicylic acid, C9 H8 O4 . This organic acid was found in leaves from the willow tree, and has been used for its health effects for at least 2,400 years. Medicines made from willow and other salicylate-rich plants appear in clay tablets from ancient Sumer as well as the Ebers papyrus from ancient Egypt. Hippocrates (around 400 BC) referred to the use of salicylic tea to reduce fevers. Aspirin has been manufactured since 1899 by the German company Bayer. There are many generic varieties of aspirin. A generic drug manufacturer must prove that their product contains the same active ingredient(s) as the brand name product. Aspirin can be used to fight a host of health problems: cerebral thromboses (with less than one tablet a day); general pain or fever (two to six tablets a day); and diseases such as rheumatic fever, gout, and rheumatoid arthritis. The drug is also beneficial in helping to ward off heart attacks. In addition, biologists use aspirin to interfere with white blood cell action, and molecular biologists use the drug to activate genes. The wide range of effects that aspirin can produce made it difficult to pinpoint how it actually works, and it wasn't until
  • 48. the 1970s that biologists hypothesized that aspirin and related drugs (such as ibuprofen) work by inhibiting the synthesis of certain hormones that cause pain and inflammation. [Hormones are regulatory substances produced in an organism and transported in tissue fluids such as blood or sap to stimulate specific cells or tissues into action.] Since then, scientists have made further progress in understanding how aspirin works. They now know, for instance, that aspirin and its relatives actually prevent the growth of cells that cause inflammation. As a further example of how a change in a single functional group (See Lecture 5) can change the chemical, physical and physiological properties of a molecule, note that both aspirin and oil of wintergreen are synthesized from the same precursor, salicilic acid. See structure and reactions below. Autonomic nervous system drugs The autonomic nervous system controls the involuntary processes of the glands, large internal organs, cardiac muscle, and blood vessels. It is divided functionally and anatomically into the sympathetic and the parasympathetic systems, which are associated with the fight-or-flight response or with rest and energy conservation, respectively. Organization of the autonomic nervous system.Encyclopædia Britannica, Inc. Modern pharmacological understanding of the autonomic nervous system emerged from several key insights made in the early 20th century. The first of these came in 1914, when British physiologist Sir Henry Dale suggested that acetylcholine was the neurotransmitter at the synapse between
  • 49. preganglionic and postganglionic sympathetic neurons and also at the ends of postganglionic, parasympathetic nerves. Preganglionic neurons originate in the central nervous system, whereas postganglionic neurons lie outside the central nervous system. Dale showed that acetylcholine could produce many of the same effects as direct stimulation of parasympathetic nerves. Firm evidence that acetylcholine was in fact the neurotransmitter emerged in 1921, when German physiologist Otto Loewi discovered that stimulation of the autonomic nerves to the heart of a frog caused the release of a substance, later identified to be acetylcholine, which slowed the beat of a second heart perfused with fluid from the first. Similar direct evidence of the release of a sympathetic neurotransmitter, later shown to be norepinephrine (noradrenaline), was obtained by American physiologist Walter Cannon in 1921. Norepinephrine
  • 50. Both acetylcholine and norepinephrine act on more than one type of receptor. Dale found that two foreign substances, nicotine and muscarine, could each mimic some, but not all, of the parasympathetic effects of acetylcholine. The structure of muscarine is given below, that of nicotin later in this Lecture. Muscarine Nicotine stimulates skeletal muscle and sympathetic ganglia cells. Muscarine stimulates receptor sites located only at the junction between postganglionic parasympathetic neurons and the target organ. Muscarine slows the heart, increases the secretion of body fluids, and prepares the body for digestion. Dale therefore classified the many actions of acetylcholine into nicotinic effects and muscarinic effects. Drugs that influence the activity of acetylcholine, including atropine, scopolamine, and tubocuraine, are known as cholinergic drugs (see later text).
  • 51. A similar analysis of the sympathetic effects of norepinephrine, epinephrine, and related drugs was carried out by American pharmacologist Raymond Ahlquist, who suggested that these agents acted on two principal receptors. A receptor that is activated by the neurotransmitter released by an adrenergic neuron is said to be an adrenoceptor. Ahlquist called the two kinds of adrenoceptor alpha (α) and beta (β). This theory was confirmed when Sir James Black developed a new type of drug that was selective for the β-adrenoceptor. Adrenoline is a hormone secreted by the adrenal glands, especially in conditions of stress, increasing rates of blood circulation, breathing, and carbohydrate metabolism and preparing muscles for exertion. α-adrenoceptors and β-adrenoceptors are divided into subclasses: α1 ,α2 and β1, β2, β3. These receptor subtypes were recognized by their responses to specific agonists and antagonists, which provided important
  • 52. leads for the development of new drugs. For example, salbutamol was discovered as a specific β2-adrenoceptor agonist. It is used to treat asthma and is a great improvement over its predecessor, isoproterenol. Because the activity of isoproterenol is not specific, it acts on β1-adrenoceptors as well as β2-adrenoceptors, resulting in cardiac effects that are sometimes dangerous. Salbutamol and other agents that act on adrenoceptors, including albuterol, ephedrine, and imipramine, are known as adrenergic drugs. Central nervous system drugsSeveral major groups of drugs, notably anethetics and psychiatric drugs, affect the central nervous system. These agents often are administered in order to produce changes in physical sensation, behavior, or mental state. General anesthetics induce a temporary loss of consciousness, enabling surgeons to operate on a patient without the patient’s feeling pain. Local anesthetics induce a loss of sensation in just one area of the body by blocking conduction in nerves at and near the injection site.Drugs that influence the operation of neurotransmitter systems in the brain can profoundly influence and alter the behavior of patients with mental disorders. Psychiatric drugs that affect mood and behavior may be classified as antidepressants, antianxiety agents, antipsychotics or antimanics. What is a hallucinogen? A hallucinogen is a psychoactive agent that often causes hallucinations, perceptual anomalies, and other substantial subjective changes in thought, emotion, and consciousness that are not typically experienced to such degrees with other categories of drugs. Research suggests that classic hallucinogens work at least partially by temporarily
  • 53. disrupting communication between brain chemical systems throughout the brain and spinal cord. Some hallucinogens interfere with the action of the brain chemical serotonin, which regulates mood and sensory perception. Serotonin What are some common hallucinogens? Caffine Caffeine is a central nervous system (CNS) stimulant. It is the world's most widely consumed psychoactive drug. Unlike many other psychoactive substances, it is legal and unregulated in nearly all parts of the world. There are several known mechanisms to explain the effects of caffeine. The most prominent is that it reversibly blocks the action of adenosine on its receptors and consequently prevents the onset of drowsiness induced by adenosine. Caffeine also stimulates certain portions of the autonomic nervous system. Nicotine Nicotine is a stimulant (alkaloid) that is naturally produced in the nightshade family of plants. It is highly addictive. Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors, except at two nicotinic receptor subunits where it acts as a receptor antagonist. Marijuana (Cannabis)
  • 54. Marijuana is a psychoactive drug from the Cannabis plant used primarily for medical or recreational purposes. The main psychoactive component of cannabis is tetrahydrocannabinol, which is one of the 483 known compounds in the plant, including at least 65 other cannabinoids. Cocaine Cocaine, also known as coke, is a strong stimulant. Mental effects may include loss of contact with reality, an intense feeling of happiness or agitation. Physical symptoms may include a fast heart rate, sweating and large pupils. High doses can result in very high blood pressure or body temperature. Effects begin within seconds to minutes of use and last between five and ninety minutes. Cocaine has a small number of accepted medical uses such a numbing and decreasing bleeding during nasal surgery. Cocaine is addictive due to its effect on the reward pathway in the brain. Colombia, Peru and Bolivia are the most important cocaine- producing countries. What is an opioid? Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use disorder, reversing opioid overdose, suppressing cough, as well as for executions in the US. Extremely potent opioids such as carfentanil are approved only for veterinary use. Opioids are
  • 55. also frequently used non-medically for their euphoric effects or to prevent withdrawal. Side effects of opioids may include: itchiness, sedation, respiratory depression, constipation, and euphoria. Long-term use can cause tolerance, meaning that increased doses are required to achieve the same effect, and physical dependence, meaning that abruptly discontinuing the drug leads to unpleasant withdrawal symptoms. The euphoria attracts recreational use and frequent, escalating recreational use of opioids typically results in addiction. An overdose or concurrent use with other depressant drugs like benzodiazepine commonly results in death from respiratory depression. Opioids act by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract. These receptors mediate both the psychoactive and the somatic effects of opioids. Opioid drugs include partial agonists, like the anti-diarrhea drug loperamide and atagonists like naloxegol for opioid-induced constipation, which do not cross the blood-brain barrier but can displace other opioids from binding to those receptors. What are some examples of opioids?
  • 56. Morphine Morphine is found naturally in a number of plants and animals, including humans. It acts directly on the central nervous system (CNS) to decrease the feeling of pain. It can be taken for both acute pain and chronic pain. It is frequently used for pain from myocardial infarction and during labor. After injection, maximum effect is reached after about 20 minutes when given intravenously and after 60 minutes when given by mouth, while duration of effect is 3–7 hours. Potentially serious side effects include decreased respiratory effort and low blood pressure. Morphine is addictive and prone to abuse. Heroin
  • 57. Heroin is a highly addictive drug processed from morphine, a naturally occurring substance extracted from the seed pod of certain varieties of poppy plants.Common side effects include decreased breathing, dry mouth, drowsiness, impaired mental function, constipation, and addiction. Side effects of use by injection can include abscesses, infected heart valves and pneumonia.Opium (or “poppy tears”, scientific name: Lachryma papaveris) is dried latex obtained from the seed capsules of the opium poppy Papaver somniferum. Opium poppy seed pod exuding latex from a cu Approximately 12 percent of opium is made up of morphine, which is processed chemically to produce heroin and other synthetic opioids for medicinal use and for illegal drug trade. The latex also contains the closely related opiates codeine, and non-analfesic alkaloids such as papaverine and noscapine.The super sleuth, Sherlock Holmes (Robert Downey Jr. in the movies), occasionally used addictive drugs, especially in the absence of stimulating cases. He sometimes used morphine and other times cocaine. Both drugs were legal in 19th-century England. His sidekick, Dr. John Watson (Jude Law), strongly disapproved of his friend's cocaine habit, describing it as the detective's only vice, and was concerned about its effect on Holmes's mental health and intellect. Carfentanil