2. Biochemistry: Introduction
What is biochemistry?
What is biochemistry?
By the end of this course you should
be able to construct your own
definition; but for now:
Biochemistry is the study of
chemical reactions in living tissue.
3. Biochemistry: Introduction
Plans
Plans
What is biochemistry?
Cells
Cell components
Organic and
biochemistry
Concepts from organic
chemistry to remember
Small molecules and
macromolecules
Classes of small
molecules
Classes of
macromolecules
Water
Catalysis
Energetics
Regulation
Molecular biology
Evolution
4. Biochemistry: Introduction
What will we study?
What will we study?
Biochemistry is the study of chemical
reactions in living tissue, both within cells and
in intercellular media.
As such, it concerns itself with a variety of
specific topics:
5. Biochemistry: Introduction
Topics in biochemistry
Topics in biochemistry
What reactions occur;
The equilibrium energetics and kinetics of those
reactions;
How the reactions are controlled, at the chemical and
cellular or organellar levels;
How the reactions are organized to enable biological
function within the cell and in tissues and organisms.
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Organic and biological chemistry
Organic and biological chemistry
Most molecules in living things
(other than H2O, O2, and CO2)
contain C-C or C-H bonds, so
biochemistry depends heavily on
organic chemistry
But the range of organic reactions
that occur in biological systems is
fairly limited compared to the full
range of organic reactions:
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Why we use only a subset of
Why we use only a subset of
organic chemistry in biochemistry
organic chemistry in biochemistry
Biochemical reactions are
almost always aqueous.
They occur within a narrow temperature and
pressure range.
They occur within narrowly buffered pH ranges.
Many of the complex reaction mechanisms
discovered and exploited by organic chemists since
the 1860's have no counterparts in the biochemical
universe.
Frederich
Wöhler
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Cells
Cells
Most biochemical reactions (but not all!)
take place within semi-independent
biological entities known as cells
Cells in general contain replicative and
protein-synthetic machinery in order to
reproduce and survive
They often exchange nutrients and
information with other cells
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Cell components
Cell components
Cells are separated from their
environments via a selectively porous
membrane
Individual components (often called
organelles) within the cell may also
have membranes separating them from
the bulk cytosol and from one another
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Eukaryotes and prokaryotes
Eukaryotes and prokaryotes
The lowest-level distinction among
organisms is on the basis of whether
their cells have defined nuclei or not
Cells with nuclei are eukaryotic
Cells without nuclei are prokaryotic
Eubacteria and archaea are prokaryotic
Other organisms (including some
unicellular ones!) are eukaryotic
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Eukaryotic organelles I
Eukaryotic organelles I
Nucleus: contains genetic information;
site for replication and transcription
Endoplasmic reticulum: site for protein
synthesis and protein processing
Ribosome: protein-synthetic machine
Golgi apparatus: site for packaging
proteins for secretion and delivery
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Eukaryotic organelles II
Eukaryotic organelles II
Mitochondrion: site for most energy-
producing reactions
Lysosome: digests materials during
endocytosis and cellular degradation
Peroxisome: site for oxidation of some
nutrients and detoxification of the H2O2
created thereby
Cytoskeleton: network of filaments that
define the shape and mobility of a cell
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Eukaryotic organelles III
Eukaryotic organelles III
Chloroplast: site for most
photosynthetic reactions
Vacuoles: sacs for water or other
nutrients
Cell wall: bacterial or plant component
outside cell membrane that provides
rigidity and protection against osmotic
shock
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Concepts from organic chemistry
There are some elements of organic
chemistry that you should have clear in your
minds.
All of these are concepts with significance
outside of biochemistry, but they do play
important roles in biochemistry.
If any of these concepts is less than
thoroughly familiar, please review it:
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Organic
Organic
concepts I
concepts I
Covalent bond: A strong attractive interaction
between neighboring atoms in which a pair of
electrons is roughly equally shared between
the two atoms.
– Covalent bonds may be single bonds, in which
one pair of electrons is shared; double bonds,
which involve two pairs of electrons; or triple
bonds, which involve three pairs (see above).
– Single bonds do not restrict the rotation of other
substituents around the bond; double and triple
bonds do.
Image courtesy Michigan State U.
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Organic concepts II
Organic concepts II
Ionic bond: a strong
attractive interaction
between atoms in
which one atom or
group is positively
charged, and another
is negatively charged.
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Organic concepts III
Organic concepts III
Hydrogen bond: A weak attractive
interaction between neighboring atoms in
which a hydrogen atom carrying a slight,
partial positive charge shares that positive
charge with a neighboring electronegative
atom.
– The non-hydrogen atom to which the hydrogen
is covalently bonded is called the hydrogen-
bond donor;
– the neighboring atom that takes on a bit of the
charge is called the hydrogen-bond acceptor
Cartoon
courtesy
CUNY
Brooklyn
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Organic
Organic
concepts IV
concepts IV
Van der Waals
interaction:
A weak attractive
interaction between
nonpolar atoms,
arising from
transient induced
dipoles in the two
atoms. Image courtesy
Columbia U. Biology Dept.
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Organic
Organic
Concepts V
Concepts V
Chirality: The property of
a molecule under which it
cannot be superimposed
upon its mirror image.
Image courtesy DRECAM, France
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Organic
Organic
Concepts VI
Concepts VI
Tautomerization: The interconversion of two
covalently different forms of a molecule via a
unimolecular reaction that proceeds with a low
activation energy. The two forms of the
molecule are known as tautomers: because of
the low activation barrier between the two forms,
we will typically find both species present.
acetone
propen-2-ol
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Organic Concepts
Organic Concepts
VII
VII
Nucleophilic substitution: a
reaction in which an electron-rich
(nucleophilic) molecule attacks an
electron-poor (electrophilic)
molecule and replaces group or
atom within the attacked species.
– The displaced group is known as a
leaving group.
– This is one of several types of
substitution reactions, and it occurs
constantly in biological systems.
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Organic Concepts VIII
Organic Concepts VIII
Polymerization: creation of large
molecules by sequential addition of simple
building blocks
– often by dehydration, i.e., the elimination of
water from two species to form a larger one:
R1-O-H + HO-R2-X-H → R1-X-R2-OH + H2O
– The product here can then react with
HO-R3-X-H to form
R1-X-R2-X-R3-OH with elimination of another
water molecule, and so on.
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Organic Concepts IX
Organic Concepts IX
Equilibrium: in the context of a chemical
reaction, the state in which the concentrations
of reactants and products are no longer
changing with time because the rate of
reaction in one direction is equal to the rate in
the opposite direction.
Kinetics: the study of the rates at which
reactions proceed.
Conventionally, we use the term
thermodynamics to describe our
understanding of the energetics of equilibrium
systems
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Organic Concepts X
Organic Concepts X
Catalysis: the lowering of the energetic barrier
between substrates and products in a reaction by the
participation of a substance that ultimately is
unchanged by the reaction
– It is crucial to recognize that catalysts (chemical agents that
perform catalysis) do not change the equilibrium position of
the reactions in which they participate:
– they only change the rates (the kinetics) of the reactions
they catalyze.
Zwitterion: a compound containing both a positive
and a negative charge
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Classes of small molecules
Classes of small molecules
Small molecules other than
water make up a small
percentage of a cell's mass, but
small molecules have significant
roles in the cell, both on their
own and as building blocks of
macromolecules. The classes of
small molecules that play
significant roles in biology are
listed below. In this list, "soluble"
means "water-soluble".
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iClicker quiz (for attendance)
iClicker quiz (for attendance)
How many midterms will we have?
(a) 1
(b) 2
(c ) 3
(d) 4
(e) I don’t care.
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Biological small molecules I
Biological small molecules I
Water: Hydrogen hydroxide. In liquid form in
biological systems. See below.
Lipids: Hydrophobic molecules, containing
either alkyl chains or fused-ring structures. A
biological lipid usually contains at least one
highly hydrophobic moeity.
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Biological small molecules II
Biological small molecules II
Carbohydrates: Polyhydroxylated
compounds for which the building
blocks are highly soluble.
– The typical molecular formula for the
monomeric forms of these compounds is
(CH2O)n, where 3 < n < 9,
– but usually n = 5 or 6.
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Biological small molecules III
Biological small molecules III
Amino acids: Compounds containing an
amine (NH3
+
) group and a carboxyl (COO-
)
group.
The most important biological amino acids
are α-amino acids, in which the amine
group and the carboxyl group are separated
by one carbon, and that intervening carbon
has a hydrogen attached to it. Thus the
general formula for an α-amino acid is
H3N+
- CHR - COO-
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Biological small
Biological small
molecules IV
molecules IV
Nucleic acids: Soluble compounds that
include a nitrogen-containing ring system.
– The ring systems are derived either from purine or
pyrimidine.
– The most important biological nucleic acids are
those in which the ring system is covalently
attached to a five-carbon sugar, ribose, usually
with a phosphate group attached to the same
ribose ring.
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Small molecules V
Small molecules V
Inorganic ions: Ionic species containing no
carbon but containing one or more atoms and
at least one net charge.
– Ions of biological significance include
Cl-
, Na+
, K+
, Mg+2
, Mn+2
, I-
, Ca+2
, PO4
-3
, SO4
-2
, NO3
-
, NO2
-
,
and NH4
+
.
– Phosphate (PO4
-3
) is often found in partially
protonated forms HPO4
-2
and H2PO4
-
– Ammonium ions occasionally appear as neutral
ammonia (NH3), particularly at higher pH values
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Biological Small Molecules VI
Biological Small Molecules VI
Cofactors: This is a catchall category for organic
small molecules that serve in some functional role in
biological organisms. Many are vitamins or are
derived from vitamins; a vitamin is defined as an
organic molecule that is necessary for metabolism
but cannot be synthesized by the organism. Thus the
same compound may be a vitamin for one organism
and not for another.
Ascorbate (vitamin C) is a vitamin for humans and
guinea pigs but not for most other mammals.
Cofactors often end up as prosthetic groups,
covalently or noncovalently attached to proteins and
involved in those proteins' functions.
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Biological
Biological
macromolecules
macromolecules
Most big biological
molecules are polymers, i.e.
molecules made up of large
numbers of relatively simple
building blocks.
Cobalamin is the biggest
nonpolymeric biomolecule I
can think of (MW 1356 Da)
Structure
courtesy
Wikimedia
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Categories of biological
Categories of biological
polymers
polymers
Proteins
Nucleic acids
Polysaccharides
Lipids (sort of):
– 2-3 chains of aliphatics attached to a
polar head group, often built on glycerol
– Aliphatic chains are usually 11-23 C’s
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Polymers and oligomers
Polymers and oligomers
These are distinguished only by the
number of building-blocks contained
within the multimer
Oligomers: typically < 50 building
blocks
Polymers ≥ 50 building blocks.
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Categories of biopolymers
Categories of biopolymers
Category # mono-
mers
<mol wt/
monomer>
# mono-
mers
Branch-
ing?
Protein 20 110 65-5000 no
RNA 4-10 220-400 50-15K no
DNA 4 200-400 50-106
no
Polysac-
charide
~10 180 2-105
Some-
times
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Water: a complex substance
Water: a complex substance
Oxygen atom is covalently bonded to 2
hydrogens
Single bond character of these bonds means
the H-O-H bond angle is close to 109.5º =
acos(-1/3): actually more like 104.5º
This contrasts with O=C=O (angle=180º) or
urea ((NH2)2-C=O) (angles=120º)
Two lone pairs available per oxygen:
these are available as H-bond acceptors
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Water is polar
Water is polar
Charge is somewhat unequally shared
Small positive charge on H’s (δ+
); small
negative charge on O (2δ-
) (Why?)
A water molecule will orient itself to align
partial negative charge on one molecule
close to partial positive charges on
another.
Hydrogen bonds are involved in this.
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Liquid water is mobile
Liquid water is mobile
The hydrogen-bond networks
created among water molecules
change constantly on a sub-
picosecond time scale
At any moment the H-bonds look like
those in crystalline ice
Solutes disrupt the H-bond networks
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Water in reactions
Water in reactions
Water is a medium within which reactions
occur;
But it also participates in reactions
Enzymes often function by making water
oxygen atoms better nucleophiles or water
H’s better electrophiles
Therefore water is a direct participant in
reactions that wouldn’t work in a
nonenzymatic lab setting!
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Water’s physical properties
Water’s physical properties
High heat capacity:
stabilizes temperature in living
things
High surface tension
Nearly incompressible (density
almost independent of pressure)
Density max at 3.98ºC
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Catalysis
Catalysis
Catalysis is the lowering of the
activation energy barrier between
reactants and products
How?
– Physical surface on which reactants can
be exposed to one another
– Providing moieties that can temporarily
participate in the reaction and be
restored to their original state at the end
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Biological catalysts
Biological catalysts
1890’s: Fischer realized that there had
to be catalysts in biological systems
1920’s: Sumner said they were
proteins
It took another 10 years for
the whole community to accept that
It’s now known that RNA can be
catalytic too:
– Can catalyze modifications in itself
– Catalyzes the key step in protein
synthesis in the ribosome
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Energy in biological systems
Energy in biological systems
We distinguish between
thermodynamics and kinetics:
Thermodynamics characterizes the
energy associated with equilibrium
conditions in reactions
Kinetics describes the rate at which a
reaction moves toward equilibrium
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Thermodynamics
Thermodynamics
Equilibrium constant is a measure of
the ratio of product concentrations
to reactant concentrations at
equilibrium
Free energy is a measure of the
available energy in the products and
reactants
They’re related by ∆Go
= -RT ln Keq
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Kinetics
Kinetics
Rate of reaction is dependent
on Kelvin temperature T and
on activation barrier ∆G‡
preventing conversion from
one site to the other
Rate = Qexp(-∆G‡
/RT)
Job of an enzyme is to reduce
∆G‡
Svante Arrhenius
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Regulation
Regulation
Biological reactions are regulated in the
sense that they’re catalyzed by enzymes, so
the presence or absence of the enzyme
determines whether the reaction will proceed
The enzymes themselves are subject to
extensive regulation so that the right
reactions occur in the right places and times
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Typical enzymatic regulation
Typical enzymatic regulation
Suppose enzymes are involved in converting A to
B, B to C, C to D, and D to F. E is the enzyme that
converts A to B:
(E)
A → B → C → D → F
In many instance F will inhibit (interfere) with the
reaction that converts A to B by binding to a site
on enzyme E so that it can’t bind A.
This feedback inhibition helps to prevent
overproduction of F—homeostasis.
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Molecular biology
Molecular biology
This phrase means something much more
specific than biochemistry:
It’s the chemistry of replication, transcription,
and translation, i.e., the ways that genes are
reproduced and expressed.
Most of you have taken biology 214 or its
equivalent; we’ll review some of the contents
of that course here, mostly near the end of the
semester.
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The molecules of
The molecules of
molecular biology
molecular biology
Deoxyribonucleic acid: polymer; backbone is
deoxyribose-phosphate; side chains are
nitrogenous ring compounds
RNA: polymer; backbone is ribose-
phosphate; side chains as above
Protein: polymer: backbone is
NH-(CHR)-CO; side chains are 20
ribosomally encoded styles
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Steps in molecular biology:
Steps in molecular biology:
the
the Central Dogma
Central Dogma
DNA replication (makes accurate copy of
existing double-stranded DNA prior to
mitosis)
Transcription (RNA version of DNA message
is created)
Translation (mRNA copy of gene serves as
template for making protein: 3 bases of RNA
per amino acid of synthesized protein)
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Evolution and Taxonomy
Evolution and Taxonomy
Traditional studies of interrelatedness of
organisms focused on functional similarities
This enables production of phylogenetic trees
Molecular biology provides an alternative,
possibly more quantitative, approach to
phylogenetic tree-building
More rigorous hypothesis-testing possible
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Quantitation
Quantitation
Biochemistry is a quantitative science.
Results in biochemistry are rarely significant unless
they can be couched in quantifiable terms.
Thermodynamic & kinetic behavior of biochemical
systems must be described quantitatively.
Even the descriptive aspects of biochemistry, e.g. the
compartmentalization of reactions and metabolites
into cells and into particular parts of cells, must be
characterized numerically.
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Mathematics in biochemistry
Mathematics in biochemistry
Ooo: I went into biology rather than
physics because I don’t like math
Too bad. You need some here:
but not much.
Biggest problem in past years:
exponentials and logarithms
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Exponentials
Exponentials
Many important biochemical equations are
expressed in the form
Y = ef(x)
… which can also be written
Y = exp(f(x))
The number e is the base of the natural
logarithm system and is, very roughly,
2.718281828459045
I.e., it’s 2.7 1828 1828 45 90 45
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Logarithms
Logarithms
First developed as computational tools
because they convert multiplication
problems into addition problems
They have a fundamental connection
with raising a value to a power:
Y = xa
⇔ logx(Y) = a
In particular, Y = exp(a) = ea
⇔
lnY = loge(Y) = a
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Course structure
Course structure
Two midterms plus a final
All exams will be closed-book, closed-notes
exams. Calculators are not allowed.
Each exam will be accompanied by a help-
sheet with many helpful facts
Gauge your memorization with the help-sheet
before you: what’s on the help sheet doesn’t
need to be memorized
My exams tend to be long but easy:
budget your time carefully!
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Grading
Grading
I’m a moderately tough grader, but I do curve
this course
The cutoff for an A is likely to be around an
82, but it’s uncertain
Homework, literature assignments, iClicker
quizzes, and discussion-board participation
count
Internet students will get a substitute
assignment to replace iClicker quizzes
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Textbook and Lecture Notes
Textbook and Lecture Notes
Garrett & Grisham is a detail-rich and
well-written text: read it!
Many of my lectures are derived from
Horton et al rather than from Garrett &
Grisham, particularly in the version that
I’ve already posted to the Internet
Be prepared for the lecture notes
themselves to evolve during the course
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Office Hours
Office Hours
I should be available 3:30-5pm
Tuesdays and Thursdays in most cases
If that doesn’t work, make an
appointment
The discussion board is another good
way to reach me and the rest of the
class as well!
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Assignments
Assignments
Regular homeworks will be due weekly,
probably on Fridays
But no assignment due tomorrow
Literature assignments are due weekly,
probably on Tuesdays
Specific readings already posted will be
augmented but not deleted