The gradient consists of two parts, the electrical potential and a difference in the chemical concentration across a membrane.
In biological processes, the direction an ion moves by diffusion or active transport across a membrane is determined by the electrochemical gradient.
Generally compound moves from an area of high concentration to low concentration (or concentration gradient). All compounds permeable to the phospholipid bilayer will move this way.
This Power Point Presentation (PPT) entitled “ Structure and Function of Lysosome”includes 43 slides with following sub- heads.
DEFINITION
INTRODUCTION/ STRUCTURE OF LYSOSOME
DISCOVERY OF LYSOSOME
DISTRIBUTION/LOCATION OF LYSOSOME
ORIGIN/ SYNTHESIS OF LYSOSOME
SHAPE AND SIZE OF LYSOSOME
CHEMICAL COMPOSITION OF LYSOSOME
LYSOSOMES ARE KNOWN AS SUICIDE BAGS
HOW THE CELL IS PROTECTED FROM LYSOSOME RUPTURE
COMMON FUNCTION OF LYSOSOME
TYPES OF LYSOSOME
DISORDERS IN HUMAN RELATED WITH LYSOSOME
SUMMARY
QUESTIONS
BOOKS CONSULTED
REFERENCES
This Power Point Presentation (PPT) entitled “ Structure and Function of Lysosome”includes 43 slides with following sub- heads.
DEFINITION
INTRODUCTION/ STRUCTURE OF LYSOSOME
DISCOVERY OF LYSOSOME
DISTRIBUTION/LOCATION OF LYSOSOME
ORIGIN/ SYNTHESIS OF LYSOSOME
SHAPE AND SIZE OF LYSOSOME
CHEMICAL COMPOSITION OF LYSOSOME
LYSOSOMES ARE KNOWN AS SUICIDE BAGS
HOW THE CELL IS PROTECTED FROM LYSOSOME RUPTURE
COMMON FUNCTION OF LYSOSOME
TYPES OF LYSOSOME
DISORDERS IN HUMAN RELATED WITH LYSOSOME
SUMMARY
QUESTIONS
BOOKS CONSULTED
REFERENCES
In cellular biology, membrane transport refers to the collection of mechanisms that regulate the passage of solutes such as ions and small molecules through biological membranes, which are lipid bilayers that contain proteins embedded in them.
explain the types and the formation of vesicles.for downloading the presentation ,more presentations , infographics and blogs visit :
https://studyscienceblog.wordpress.com
endocytosis and exocytosis is a procss of cell eating and drinnking. it is a mazor tool for self defence to an individual cell. there are some molecular mechanism for this process described in given notes.
Transport across cell membrane, CELL MEMBRANERajshri Ghogare
Transport across cell membrane, Active transport, Active transport,
Types of passive transport-Diffusion, Filtration, Osmosis, Facilitated diffusion , Types of active transport antiport and symport
In cellular biology, membrane transport refers to the collection of mechanisms that regulate the passage of solutes such as ions and small molecules through biological membranes, which are lipid bilayers that contain proteins embedded in them.
explain the types and the formation of vesicles.for downloading the presentation ,more presentations , infographics and blogs visit :
https://studyscienceblog.wordpress.com
endocytosis and exocytosis is a procss of cell eating and drinnking. it is a mazor tool for self defence to an individual cell. there are some molecular mechanism for this process described in given notes.
Transport across cell membrane, CELL MEMBRANERajshri Ghogare
Transport across cell membrane, Active transport, Active transport,
Types of passive transport-Diffusion, Filtration, Osmosis, Facilitated diffusion , Types of active transport antiport and symport
Transport through Cell Membrane including passive transport and Active transport ,special types of passive transport , Special types of active transport , Dynamic motors, lipid layer and Protein Layer
Virus, infectious agent of small size and simple composition that can multiply only in living cells of animals, plants, or bacteria. The name is from a Latin word meaning “slimy liquid” or “poison.”
Mycology is the branch of biology concerned with the study of fungi, including their genetic and biochemical properties, their taxonomy and their use to humans as a source for tinder, traditional medicine, food, and entheogens, as well as their dangers, such as toxicity or infection.
In the late 16th century several Dutch lens makers designed devices that magnified objects, but in 1609 Galileo Galilei perfected the first device known as a microscope. Dutch spectacle makers Zaccharias Janssen and Hans Lipperhey are noted as the first men to develop the concept of the compound microscope.
In the late 16th century several Dutch lens makers designed devices that magnified objects, but in 1609 Galileo Galilei perfected the first device known as a microscope. Dutch spectacle makers Zaccharias Janssen and Hans Lipperhey are noted as the first men to develop the concept of the compound microscope.
Microbial Spoilage include the contamination of Pharmaceutical products with the microbes which lead to spoilage of the product affecting Drug safety and quality, and is not intended for use. Shortly Microbial Spoilage is defined as deterioration of pharmaceutical products by the contaminant microbe.
In the late 16th century several Dutch lens makers designed devices that magnified objects, but in 1609 Galileo Galilei perfected the first device known as a microscope. Dutch spectacle makers Zaccharias Janssen and Hans Lipperhey are noted as the first men to develop the concept of the compound microscope.
Bacteria are a type of biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a number of shapes, ranging from spheres to rods and spirals. Bacteria were among the first life forms to appear on Earth, and are present in most of its habitats
Microbiology is the study of organisms that are usually too small to be seen by the unaided eye; it employs techniques—such as sterilization and the use of culture media—that are required to isolate and grow these microorganisms.
Bacteria have existed from very early in the history of life on Earth. Bacteria fossils discovered in rocks date from at least the Devonian Period (419.2 million to 358.9 million years ago), and there are convincing arguments that bacteria have been present since early Precambrian time, about 3.5 billion years ago.
Bacteria are microscopic, single-celled organisms that thrive in diverse environments. These organisms can live in soil, the ocean and inside the human gut. Humans' relationship with bacteria is complex. Sometimes bacteria lend us a helping hand, such as by curdling milk into yogurt or helping with our digestion
Bacteria are microscopic, single-celled organisms that thrive in diverse environments. These organisms can live in soil, the ocean and inside the human gut. Humans' relationship with bacteria is complex. Sometimes bacteria lend us a helping hand, such as by curdling milk into yogurt or helping with our digestion
Diuretics, also called water pills, are medications designed to increase the amount of water and salt expelled from the body as urine. There are three types of prescription diuretics. They're often prescribed to help treat high blood pressure, but they're used for other conditions as well.
The main site of diuretic action is well established for the different groups of diuretics: carbonic anhydrase inhibitors act on the proximal tubulus, loop diuretics on the diluting segment, thiazides on the cortical diluting segment/distal tubulus, and potassium-sparing agents on distal tubulus/collecting ducts.
Diuretics, also called water pills, are medications designed to increase the amount of water and salt expelled from the body as urine. There are three types of prescription diuretics. They’re often prescribed to help treat high blood pressure, but they’re used for other conditions as well.
Proton-pump inhibitors are a group of medications whose main action is a pronounced and long-lasting reduction of stomach acid production. Within the class of medications, there is no clear evidence that one agent works better than another. They are the most potent inhibitors of acid secretion available.
The main site of diuretic action is well established for the different groups of diuretics: carbonic anhydrase inhibitors act on the proximal tubulus, loop diuretics on the diluting segment, thiazides on the cortical diluting segment/distal tubulus, and potassium-sparing agents on distal tubulus/collecting ducts.
In conclusion, the present study found that esomeprazole 40 mg daily may be more effective than either omeprazole 20 mg daily, pantoprazole 40 mg daily or lansoprazole 30 mg daily for the rapid relief of heartburn symptoms in patients with endoscopically proven reflux esophagitis.
Mechanisms of diuretic drugs. Diuretic drugs increase urine output by the kidney (i.e., promote diuresis). This is accomplished by altering how the kidney handles sodium. If the kidney excretes more sodium, then water excretion will also increase.
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Cell Membrane Transport/Factors/Transport of Substances
1. MEMBRANE TRANSPORT
Md. Saiful Islam
Dept. of Pharmaceutical Sciences
North South University
Facebook Group: Pharmacy Universe
YouTube Channel: Pharmacy Universe
2. 1. Factors affecting transport: cell membrane
• The cell needs to absorb and
excrete various compounds
throughout its life.
These compounds need to pass
through the membrane which
is made from a phospholipid
bilayer
• The phospholipid bilayer is
formed by phospholipid
molecules bipolar
molecule: the fatty acid side is
hydrophobic, the phosphoric
side is hydrophilic
3. 2. Factors affecting transport: Electrochemical gradient
• The gradient consists of two parts, the electrical potential and a
difference in the chemical concentration across a membrane.
• In biological processes, the direction an ion moves
by diffusion or active transport across a membrane is determined by
the electrochemical gradient.
• Generally compound moves from an area of high concentration to
low concentration (or concentration gradient). All compounds
permeable to the phospholipid bilayer will move this way.
5. TRANSPORT OF SUBSTANCES THROUGH THE
CELL MEMBRANE
1. Passive transport
A. Simple diffusion
B. Facilitated diffusion
2. Active transport
6. Passive and active transport compared.
Passive transport down an electrochemical
gradient occurs spontaneously, either by
simple diffusion through the lipid bilayer or
by facilitated diffusion through channels and
passive carriers. By contrast, active
transport requires an input of metabolic
energy and is always mediated by carriers
that harvest metabolic energy to pump the
solute against its electrochemical gradient.
An electrochemical gradient combines the
membrane potential and the concentration
gradient, which can work additively to increase
the driving force on an ion across the membrane
(middle) or can work against each other (right).
7. Transport of small molecules
Gases, hydrophobic
molecules, and small
polar uncharged
molecules can
diffuse through
phospholipid
bilayers. Larger polar
molecules and
charged molecules
cannot.
8. • Osmosis is the movement of water across a selectively permeable
membrane from an area of high water potential (low solute
concentration) to an area of low water potential (high solute
concentration).
• It may also be used to describe a physical process in which any solvent moves,
without input of energy, across a semipermeable membrane (permeable to the
solvent, but not the solute) separating two solutions of different
concentrations.
Osmosis
9. Solution tonicity
• Isotonic solution: solution which
has the same compound
concentration as the cell
• Hypotonic solution: solution
having a compound in lower
concentration compared to the
cell
• Hypertonic solution: solution
having a compound in higher
concentration compared to the
cell
10. Simple diffusion
• During passive diffusion, a molecule simply
dissolves in the phospholipid bilayer and
diffuses across it
• then dissolves in the aqueous solution at the
other side of the membrane
• the direction of transport is determined simply
by the relative concentrations of the molecule
inside and outside of the cell.
• The net flow of molecules is always down their
concentration gradient from a compartment
with a high concentration to one with a lower
concentration of the molecule.
• No membrane proteins are involved
11. Facilitated Diffusion
• In facilitated diffusion molecules travel across the membrane in the
direction determined by their concentration gradients.
• Charged molecules travel across the membrane in the direction
determined by the electric potential across the membrane.
• Facilitated diffusion allows polar and charged molecules, such as
carbohydrates, amino acids, nucleosides, and ions, to cross the plasma
membrane.
• facilitated diffusion differs from passive diffusion in that the
transported molecules do not dissolve in the phospholipid bilayer.
Instead, their passage is mediated by proteins that enable the
transported molecules to cross the membrane without directly
interacting with its hydrophobic interior
12. • Glucose, sodium ions and chloride ions are just a few examples of
molecules and ions that must efficiently get across the plasma
membrane but to which the lipid bilayer of the membrane is virtually
impermeable.
• Their transport must therefore be "facilitated" by proteins that span
the membrane and provide an alternative route or bypass.
• It is similar to simple diffusion in the sense that it does not require
expenditure of metabolic energy and transport is again down an
electrochemical gradient.
FACILITATED DIFFUSION
13. • Two major groups of integral membrane
proteins are involved in facilitated diffusion:
1. Carrier proteins and 2. Ion Channels
1. Carrier proteins (also known as permeases or
transporters) bind a specific type of solute and are
thereby induced to undergo a series of
conformational changes which has the effect of
carrying the solute to the other side of the
membrane. The carrier then discharges the solute
and, through another conformational change,
reorients in the membrane to its original state.
Typically, a given carrier will transport only a small
group of related molecules.
• Some important and illustrative groups of
transporters are:
– Certain of the hexose transporters, which
transport glucose and similar
monosaccharides into and out of cells
– the anion transporter, which facilitates
transport of bicarbonate and chloride ions.
Uniporter
moves a single molecule
down its concentration
gradient
14. Classes of
carrier
proteins
Uniport Symport Antiport
A A B A
B
Uniport carriers mediate transport of a single solute.
An example is the GLUT1 glucose carrier.
Carrier proteins are integral/intrinsic membrane proteins; that is they exist
within and span the membrane across which they transport substances. The
proteins may assist in the movement of substances by facilitated
diffusion or active transport. These mechanisms of movement are known
as carrier-mediated transport.
15. Uniport Symport An
A A B
A gradient of one substrate, usually an ion, may drive uphill (against
the gradient) transport of a co-substrate.
E.g: glucose-Na+ symport, in plasma membranes
of some epithelial cells
bacterial lactose permease, a H+ symport carrier.
Symport (cotransport) carriers
bind two dissimilar solutes
(substrates) & transport them
together across a membrane.
Transport of the two solutes is
obligatorily coupled.
16. port Symport Antiport
A A B A
B
A substrate binds & is transported. Then another
substrate binds & is transported in the other direction.
Only exchange is catalyzed, not net transport.
The carrier protein cannot undergo the conformational
transition in the absence of bound substrate.
Antiport carriers exchange one solute for
another across a membrane.
Usually antiporters exhibit "ping pong"
kinetics.
Example of an antiport carrier:
Adenine nucleotide translocase (ADP/ATP exchanger) catalyzes
1:1 exchange of ADP for ATP across the inner mitochondrial
membrane.
17. Facilitated diffusion of glucose
• GLUT1 is an example of uniporter.
• The glucose transporter (GLUT1)
alternates between two
conformations in which a glucose-
binding site is alternately exposed
on the outside and the inside of the
cell.
• In the first conformation shown (A),
glucose binds to a site exposed on
the outside of the plasma
membrane.
• The transporter then undergoes a
conformational change such that
the glucose-binding site faces the
inside of the cell and glucose is
released into the cytosol (B).
• The transporter then returns to its
original conformation (C).
18. 2. Ion Channels do not really bind the solute, but are like hydrophilic pores
through the membrane that open and allow certain types of solutes, usually
inorganic ions, to pass through.
• In general, channels are quite specific for the type of solute they will
transport and transport through channels is quite a bit faster than by carrier
proteins.
• Additionally, many channels contain a "gate" which is functions to control the
channel's permeability.
• When the gate is open, the channel transports, and when the gate is closed,
the channel is closed.
• Such gates can be controlled either by voltage across the membrane (voltage-
gated channels) or have a binding site for a ligand which, when bound, causes
the channels to open (ligand-gated channels).
19. • The opening and closing of gates are controlled in two
principal ways:
• 1. Voltage gating. In this instance, the molecular
conformation of the gate responds to the electrical
potential across the cell membrane.
• For instance, when there is a strong negative charge on
the inside of the cell membrane, this presumably could
cause the outside sodium gates to remain tightly
closed;
• Conversely, when the inside of the membrane loses its
negative charge, these gates would open suddenly and
allow tremendous quantities of sodium to pass inward
through the sodium pores.
• This is the basic mechanism for eliciting action
potentials in nerves that are responsible for nerve
signals.
• the potassium gates are on the intracellular ends of the
potassium channels, and they open when the inside of
the cell membrane becomes positively charged. The
opening of these gates is partly responsible for
terminating the action potential.
20. 2. Chemical (ligand) gating. Some protein
channel gates are opened by the binding of a
chemical substance (a ligand) with the protein;
this causes a conformational or chemical
bonding change in the protein molecule that
opens or closes the gate. This is called chemical
gating or ligand gating.
• One of the most important instances of
chemical gating is the effect of acetylcholine on
the so-called acetylcholine channel.
• Acetylcholine opens the gate of this channel,
providing a negatively charged pore about 0.65
nanometer in diameter that allows uncharged
molecules or positive ions smaller than this
diameter to pass through.
• This gate is exceedingly important for the
transmission of nerve signals from one nerve
cell to another and from nerve cells to muscle
cells to cause muscle contraction.
22. • Nerve signals are transmitted by action potentials, which are rapid changes in
the membrane potential that spread rapidly along the nerve fiber membrane.
• Each action potential begins with a sudden change from the normal
resting negative membrane potential to a positive potential and
then ends with an almost equally rapid change back to the
negative potential.
• To conduct a nerve signal, the action potential moves along the nerve fiber until
it comes to the fiber’s end.
• Action potentials occur in several types of animal cells, called excitable cells,
which include neurons, muscle cells, and endocrine cells.
• In neurons, they play a central role in cell-to-cell communication.
• In other types of cells, their main function is to activate intracellular processes.
• In muscle cells, for example, an action potential is the first step in the chain of
events leading to contraction.
• In beta cells of the pancreas, they provoke release of insulin.
Action Potentials (APs)
23. Resting Membrane Potential (Vr)
• The potential difference across the
membrane of a cell.
• It is generated by different concentrations
of Na+, K+, Cl, and protein anions (A).
24. Action Potential: Resting State
• Na+ and K+ channels are
closed.
• This is the resting membrane
potential before the action
potential begins.
• The membrane is said to be
“polarized” during this stage
because of the –90 millivolts
negative membrane potential
that is present.
25. Action Potential: Depolarization Phase
• At this time, the membrane suddenly becomes very
permeable to sodium ions, allowing tremendous
numbers of positively charged sodium ions to diffuse
to the interior of the axon.
• The normal “polarized” state of –90 millivolts is
immediately neutralized by the inflowing positively
charged sodium ions, with the potential rising rapidly
in the positive direction. This is called depolarization.
• In large nerve fibers, the great excess of positive
sodium ions moving to the inside causes the
membrane potential to actually “overshoot” beyond
the zero level and to become somewhat positive. In
some smaller fibers, as well as in many central
nervous system neurons, the potential
merely approaches the zero level and does not
overshoot
to the positive state.
• Threshold – a critical level of depolarization
(-55 to -50 mV) At threshold, depolarization
becomes self-generating
Na+ permeability increases; membrane potential reverses
Na+ gates are opened; K+ gates are closed
26. Action Potential: Repolarization Phase
• Within a few 10,000ths of a
second after the membrane
becomes highly permeable to
sodium ions, the sodium
channels begin to close and the
potassium channels open more
than normal.
• Then, rapid diffusion of
potassium ions to the exterior
re-establishes the normal
negative resting membrane
potential. This is called
repolarization of the membrane
27. Phases of the Action Potential
• Changes in membrane potentials are caused by three events
– Resting Stage-Membrane potential is -90 MV
– Depolarization – the inside of the membrane becomes less negative
– Repolarization – the membrane returns to its resting membrane
potential.
28.
29. Active Transport
• The movement of across the cell
membrane against the
concentration gradient with active
expenditure of energy by the help
of carrier called active transport.The
energy is derived from ATP and
carriers are present in the cell
membrane
30. Direct Active Transport
-Primary active transport, also called direct active transport,
directly uses energy to transport molecules across a
membrane.
-Most of the enzymes that perform this type of transport are
transmembrane ATPases. A primary ATPase universal to all
cellular life is the sodium-potassium pump, which helps to
maintain the cell potential.
31. The sodium potassium pump is an active transport mechanism
that is driven by the breakdown of ATP and works through a
series of conformational change in a transmembrane protein.
Three sodium ion binds to the cytoplasm site of a protein,
causing the protein to change its conformation.
In its new conformation, the molecules become phosphorylated
at the expense of a molecule of ATP.
BOTH ARE MOVING
AGAINST THEIR
CONCENTRATION
GRADIENT
Na+/K+ ATPase
32. • The phosphorylation induces a second conformational change that translocates the
three sodium ion across the membrane.
• In this conformation protein has a low affinity for sodium ions and three bound
sodium ion dissociates from the protein and diffuse into the ECF.
• The new conformation has a high affinity for potassium ions, two of which binds to
the extracellular side of a protein.
• The bound phosphate then dissociates and protein reverts to its original
conformation, exposing two potassium ions to the cytoplasm on the inside of the cell.
• This conformation has a low affinity for potassium ions, so the two bound potassium
ions dissociate from the protein and diffuse into the interior of the cell
33. Na+/K+ ATPase
• Cycle of transport: At the starting point, the protein is open
facing the cytoplasmic side of the cell. 3Na+ molecules
bind to specific high affinity sites.
34. Na+/K+ ATPase
• Cycle of transport: Following this binding, ATP is
hyrdolyzed and a phosphate is added to the
cytoplasmic side of the protein.
35. Na+/K+ ATPase
• Cycle of transport: This induces a conformational
change which opens the protein to the extracellular
space and causes extracellular release of Na+
36. Na+/K+ ATPase
• Cycle of transport: In this conformation the protein has
high affinity for 2 molecules of K+
37. Na+/K+ ATPase
• Cycle of transport: The binding of K+ causes a release
of the phosphate group
38. Na+/K+ ATPase
• Cycle of transport: Another conformational change
occurs, which opens the protein to the cytosolic side
allowing release of the K+ on the inside of the cell
39. Electrogenic Nature of the Na+-K+ Pump. The fact that the
Na+-K+ pump moves three Na+ ions to the exterior for
every two K+ ions to the interior means that a net of one
positive charge is moved from the interior of the cell to
the exterior for each cycle of the pump.
This creates positivity outside the cell but leaves a
deficit of positive ions inside the cell; that is, it causes
negativity on the inside.
Therefore, the Na+-K+ pump is said to be electrogenic
because it creates an electrical potential across the cell
membrane.
40. Importance of the Na+-K+ Pump for Controlling Cell Volume.
One of the most important functions of the Na+-K+ pump is to
control the volume of each cell. Without function of this pump,
most cells of the body would swell until they burst. The mechanism
for controlling the volume is as follows:
Inside the cell are large numbers of proteins and other organic
molecules that cannot escape from the cell.
Most of these are negatively charged and therefore attract large
numbers of potassium, sodium, and other positive ions as well.
All these molecules and ions then cause osmosis of water to the
interior of the cell. Unless this is checked, the cell will swell
indefinitely until it bursts.
The normal mechanism for preventing this is the Na+-K+ pump.
41. ABC Transporters
• ATP-powered pump
• ABC = ATP binding cassette
• Over 100 members
• Transport ions and various molecules
• 2 transmembrane and 2 ATP binding
domains
• Medically relevant
-MDR (cancer)
42. MDR1 (ABCB1)
• Membrane proteins and disease
• MDR1—multidrug-resistance transport
protein
– Uses ATP hydrolysis to export drugs from
the cytoplasm to the extracellular medium
43. Flipase model
• Using hydrolysis of ATP, the pump flips the drug so
the hydrophilic head faces the outside of the cell
• Molecule then moves out of the transporter and
eventually out of the membrane
• Hydrophobic portion
of drug molecule
inserts in plasma
membrane
• Moves until it hits an
MDR1 ABC
transporter
44. Substrate diffuses into the membrane
Lateral association with MDR1
Promotes flipping across leaflet
Substrate associates with intracellular
domain of MDR1
MDR pumps substrate out through a
pore
MDR1 mechanism of action
45. Secondary Active Transport
In secondary active transport or co-transport, in
contrast to primary active transport, there is no
direct coupling of ATP; instead, the
electrochemical potential difference created by
pumping ions in or out of the cell is used.
The two main forms of this are antiport and
symport.
Symport:
Symport uses the downhill movement of one
solute species from high to low concentration to
move another molecule along with it.
An example is the glucose symporter SGLT1,
which co-transports one glucose (or galactose)
molecule into the cell for every two sodium ions it
imports into the cell.
This symporter is located in the small intestines,
trachea, heart, brain, testis, and prostate.
46. •When sodium ions are transported out of cells by primary active
transport, a large concentration gradient of sodium ions across the cell
membrane usually develops—high concentration outside the cell and very
low concentration inside.
•This gradient represents a storehouse of energy because the excess
sodium outside the cell membrane is always attempting to diffuse to the
interior.
• Under appropriate conditions, this diffusion energy of sodium can pull
other substances along with the sodium through the cell membrane.This
phenomenon is called co-transport; it is one form of secondary active
transport.
For sodium to pull another substance along with it, a coupling mechanism
is required. This is achieved by means of still another carrier protein in the
cell membrane.
The carrier in this instance serves as an attachment point for both the
sodium ion and the substance to be co-transported.
Once they both are attached, the energy gradient of the sodium ion causes
both the sodium ion and the other substance to be transported together to
the interior of the cell.
48. Antiport
•In antiport two species of ion or other solutes are pumped in opposite directions across a
membrane.
• One of these species is allowed to flow from high to low concentration which yields the
entropic energy to drive the transport of the other solute from other side of membrane
•An example is the sodium-calcium exchanger or antiporter, which allows three sodium ions
into the cell to transport one calcium out.
•In counter-transport, sodium ions again attempt to diffuse to the interior of the cell because
of their large concentration gradient.
• However, this time, the substance to be transported is on the inside of the cell and must be
transported to the outside.
•Therefore, the sodium ion binds to the carrier protein where it projects to the exterior
surface of the membrane, while the substance to be counter-transported binds to the interior
projection of the carrier protein.
•Once both have bound, a conformational change occurs, and energy released by the sodium
ion moving to the interior causes the other substance to move to the exterior.
49. Na+ linked Ca2+ Antiporter
• Ions move down their respective
concentration gradients
50. Na+ H+ antiporter
• The pH in cells must be
maintained as close to
neutral (~7.2)
51. Membrane assisted transports
• Special transport process for transporting
macromolecules such as-
-Proteins, polynucleotide and polysaccharides
Types:
• Exocytosis- Cell releases macromolecules to
the outside of the cell
• Endocytosis- Cell absorbs macromolecules
from the outside of the cell
52. • Exocytosis--Secretion Out side the cell
- non Ca ++ triggered -constitutive secretion
- Ca ++ triggered-regulated secretion
• Endocytosis—Absorption into the cell
– Phagocytosis— “Cell eating”
– Pinocytosis– “Cell drinking”
– Receptor-mediated endocytosis-specific particles, recognition.
Exocytosis and Endocytosis
53. Exocytosis
• Exocytosis is the process by which a cell
expels molecules and other objects that are too large to
pass through the cellular membrane
As for example: Secretion of insulin from the beta cell of
pancrease.
• Exocytosis is used for the following purposes:
• Release enzymes, hormones, proteins, and glucose to be
used in other parts of the body
• Neurotransmitters (in the case of neurons)
• Communicate defense measures against a disease
• Expel cellular waste
54. Exocytosis
• Mechanism: Macromolecules are actually
packaged in a vesicle in golgi apparatus.
• The vesicle fuses with the plasma membrane
and its contents are released without the
vesicle.
55. • In multicellular organisms there are two types
of exocytosis
(i) non Ca ++ triggered -constitutive secretion
(ii) Ca ++ triggered-regulated secretion
• Some molecules are secreted continually from the
cell, but others are selectively secreted
• Exocytosis in neuronal chemical synapses is
Ca ++ triggered and serves interneuronal signaling.
56. non Ca ++ triggered -constitutive secretion
•Some cells, such as certain white blood
cells, only secrete one type of protein. These
proteins are packaged into secretory vesicles
and sent to the cell membrane.
•Proteins destined for the constitutive
secretion pathway must first leave the
endoplasmic reticulum and pass through the
Golgi apparatus.
•If no modifications are made to the protein
while inside the Golgi, it will enter the
default secretory pathway, and the secretory
vesicle it is packaged into will be sent
directly to the cell membrane for immediate
secretion.
57. non Ca ++ triggered -constitutive secretion
•Upon reaching the cell membrane, the
secretory vesicles from the Golgi merge
with the plasma membrane of the cell by a
process called exocytosis. The cargo
proteins they contain are then released into
the extracellular matrix, and the lipids and
membrane of the vesicles are donated to the
plasma membrane.
•Certain white blood cells use the
constitutive pathway to secrete interleukins,
a kind of signaling protein used for
intercellular communication between other
white blood cells. Interleukins play an
important role in the proper function of the
immune system.
•Other cells, such as fibroblasts,
constitutively secrete proteins such as
collagen and proteoglycans and help to
maintain the structural integrity of
connective tissue.
58.
59. Ca ++ triggered-regulated secretion
•An example of a cell type that engages in the
regulated secretion of a specialized protein is the
beta cell, a type of cell found in the pancreas that
secretes insulin.
•Insulin travels from the endoplasmic reticulum
into the Golgi apparatus where it is packaged into
transport vesicles.
•Insulin undergoes several modification on its way
from the ER, through golgi, to where it is stored
for release in large secretory vescicles.
•The large vescicles are formed when many
smaller transport vescicles from the golgi fuse.
•Insulin-containing transport vesicles from the
trans Golgi-network fuse at the cell membrane for
exocytosis regulated by calcium.
60. What is Endocytosis?
• Endo (within); cytosis (cell)
• Endocytosis is a process by which cells absorb
macromolecules (such as proteins) from outside by
engulfing it with their cell membrane.
• In each case endocytosis results in the formation
of an intracellular vesicle by virtue of the
invagination of the plasma membrane and
membrane fusion.
• It is used by all cells of the body because most
substances important to them are polar and consist
of big molecules, and thus cannot pass through the
hydrophobic plasma membrane.
61. Endocytosis is used for the following purposes:
• Receive nutrients
• Entry of pathogens
• Intercellular communication
• Signal receptors
Three types of endocytosis
1. Phagocytosis
2. Pinocytosis
3. Receptor-mediated endocytosis
62. Phagocytosis
• Phagocytosis (literally, cell-eating) is the process
by which cells ingest large objects, such as
microorganisms or cell debris . The membrane
folds around the object, and the object is sealed
off into a large vacuole known as phagosome.
• In the process of phagocytosis the cell changes
shape by sending out projections which are
called pseudpodia (false feet).
• The pseudopodia then surround the particle and
when the plasma membrane of the projection
meet membrane fusion occurs.
• This results in the formation of an intracellular
vesicle.
65. Pinocytosis
• Pinocytosis (literally, cell-drinking) is a synonym for
endocytosis. This process is concerned with the
uptake of solutes and single molecules such as
proteins.
• In the process of pinocytosis the plasma membrane
froms an invagination.
• What ever substance is found within the area of
invagination is brought into the cell.
• In general this material will be dissolved in water and
thus this process is also referred to as "cellular
drinking" to indicate that liquids and material
dissolved in liquids are ingested by the cell.
• This is opposed to the ingestion of large particulate
material like bacteria or other cells or cell debris.
67. Receptor mediated endocytosis
• Receptor mediated endocytosis is an endocytotic
mechanism in which specific molecules are ingested
into the cell.
• The specificity results from a receptor-ligand
interaction.
• Receptors on the plasma membrane of the target
tissue will specifically bind to ligands on the outside
of the cell.
• An endocytotic process occurs and the ligand is
ingested.
• A very well studied example:
Metabolism of cholesterol.
68. Metabolism of cholesterol.
• Cholesterol circulates in the bloodstream and enters the cell by the
receptor-mediated endocytosis.
• Cholesterol are packed into LDL , a protein and phospholopid,particles
surrounds the cholesterol molecules
• The protein portion is recognized by LDL receptor on the surface of cells.
Adapter molecules called adaptin binds to LDL receptor that protrudes
into the cytoplasm.
• Adaptin recruits Clathrin molecule, which starts coating the molecule.
69.
70.
71. - Assembly of clathrin coat causes the membrane to bend and
invaginate and forming a vesicle that buds off into the cell along with
the cholesterol molecule.
- Inside the cell, vesicle uncoats and fuses with the endosome.
- The endosome has low pH, which causes LDL receptor to release their
cargo.
- Empty LDL receptor recycle back to plasma membrane.
- Now LDL particle needs to be disassembled and so endosomal content
delivered to the lysosome.
- Lysosome contains hydrolytic particles that digest the particles and
free cholesterol is liberated along with amino acid and peptides
generated by digestion of LDL molecules.
- The cholesterol then liberated to the cytosome to be used in the
synthesis of new membrane
Metabolism of cholesterol (Cont.)
73. Interesting information
• Eukaryotic cells are nearly continuously
ingesting the surrounding fluids and
molecules.
• In doing so they are also ingesting their
own cellular membrane at a rapid rate.
• Macrophages, for example ingest 3% of its
cellular membrane each minute, or 100%
each half and hour!
• Obviously the membrane is being added by
exocytosis at about the same rate it is being
removed by endocytosis.