Biochemistry of Cell Membrane.pptx

Rajendra Dev Bhatt
Rajendra Dev BhattAsst.Professor/Clinical Biochemist @ Dhulikhel Hospital, Kathmandu University Hospital
MEMBRANE TRANSPORT
Rajendra Dev Bhatt (PhD Scholar)
Asst. Professor
Clinical Biochemistry & Laboratory Medicine
Fellow: Translational Research (2018-2022) in CVD in
Nepal, NHLBI & NIH, USA
The plasma membrane, which is also called the cell
membrane, has many functions, but the most basic
one is to define the borders of the cell and keep the
cell functional.
The plasma membrane is selectively permeable.
This means that the membrane allows some
materials to freely enter or leave the cell, while
other materials cannot move freely, but require the
use of a specialized structure, and occasionally, even
energy investment for crossing.
Introduction
Membrane Components and
Structure
Among the most sophisticated functions of the
plasma membrane is the ability to transmit signals
by means of complex, integral proteins known as
receptors.
These proteins act both as receivers of extracellular
inputs and as activators of intracellular processes.
These membrane receptors provide extracellular
attachment sites for effectors like hormones and
growth factors, and they activate intracellular
response cascades when their effectors are bound.
Fluid Mosaic Model
The explanation proposed by Singer and Nicolson is
called the fluid mosaic model.
The model has evolved somewhat over time, but it
still best accounts for the structure and functions of
the plasma membrane as we now understand them.
The fluid mosaic model describes the structure of
the plasma membrane as a mosaic of components
including phospholipids, cholesterol, proteins, and
carbohydrates that gives the membrane a fluid
character.
Plasma membranes range from 5 to 10 nm in
thickness.
Components of a plasma
membrane
The principal components of a plasma membrane
are lipids, proteins, and carbohydrates.
The lipids include phospholipids and cholesterol
Proteins. Carbohydrate chains are attached to the
proteins and lipids on the outside surface of the
membrane.
Typical human cell, protein accounts for about 50%
of the composition by mass, lipids account for about
40% of the composition by mass, with the
remaining 10% of the com-position by mass being
carbohydrates.
The components and functions of the
plasma membrane.
Passive Transport
Passive transport is a naturally occurring
phenomenon and does not require the cell to exert
any of its energy to accomplish the movement.
In passive transport, substances move from an area
of higher concentration to an area of lower
concentration.
A physical space in which there is a range of
concentrations of a single substance is said to have
a concentration gradient.
Selective Permeability
Recall that plasma membranes are amphipathic:
They have hydrophilic and hydrophobic regions.
This characteristic helps the movement of some
materials through the membrane and hinders the
movement of others.
Lipid-soluble material with a low molecular weight
can easily slip through the hydrophobic lipid core
of the membrane. Substances such as the fat-
soluble vitamins A, D, E, and K readily pass
through the plasma membranes in the digestive
tract and other tissues.
Molecules of oxygen and carbon dioxide have no
charge and so pass through membranes by simple
diffusion.
Diffusion
• Diffusion is a passive process of transport. A
single substance tends to move from an area of
high concentration to an area of low
concentration until the concentration is equal
across a space.
Facilitated diffusion
In facilitated diffusion, materials diffuse across the
plasma membrane with the help of membrane proteins.
A concentration gradient exists that would allow these
materials to diffuse into the cell without expending
cellular energy.
However, these materials are ions or polar molecules that
are repelled by the hydrophobic parts of the cell
membrane. Facilitated diffusion proteins shield these
materials from the repulsive force of the membrane,
allowing them to diffuse into the cell.
These proteins are called transport-proteins and can be
channels or carrier proteins.
Channel proteins are trans-membrane
proteins that fold in such as way as to form a
channel or pore through the membrane. Each
channel is specific for one particular
substance.
Some channel proteins are always open but many
are “gated,” meaning that they can be opened and
closed.
If a channel is ligand-gated, the attachment of a
particular molecule to the channel protein may
cause it to open.
Other channels are voltage-gated, requiring a
change in voltage across the membrane to open
them.
Cells involved in the transmission of electrical
impulses, such as nerve and muscle cells, have
voltage-gated ion channels in their membranes.
Another type of trans-membrane transporter
protein is a carrier protein. Like channels, carrier
proteins are usually specific for particular
molecules. A carrier proteins binds a substance
and, in doing so, triggers a change of its own
shape, moving the bound molecule across the
membrane.
Osmosis
Osmosis is the diffusion of water across a
semipermeable membrane. Since it is diffusion,
it depends on the concentration gradient, or the
amount of water on each side of the membrane.
Active transport
Active transport mechanisms require the use of the cell’s
energy, usually in the form of adenosine triphosphate
(ATP).
If a substance must move into the cell against its
concentration gradient—that is, if the concentration of the
substance inside the cell is greater than its concentration
in the extracellular fluid (and vice versa)—the cell must
use energy to move the substance.
Some active transport mechanisms move small-molecular
weight materials, such as ions, through the membrane.
Other mechanisms transport much larger molecules.
Electrochemical gradient
The interior of living cells is electrically negative with
respect to the extracellular fluid surrounding them. At the
same time, cells have a lower concentration of (Na+) than
does the extracellular fluid. Therefore, both the
concentration gradient and the electrical gradient tend to
drive Na+ into the cell.
Conversely, cells have a higher concentration of K+ than
the extracellular fluid does. Therefore, the concentration
gradient tends to drive K+ out of the cell, while the
electrical gradient tends to drive it inside the cell. The
combined gradient of concentration and electrical charge
that affects an ion is called its electrochemical gradient.
Injection of a potassium solution into a
person’s blood is lethal; this is used in
capital punishment and euthanasia. Why do
you think a potassium solution injection is
lethal?
Proteins for Active Transport
The specific proteins that facilitate active transport
are called transporters. There are three types of
transporters.
A uniporter carries one specific ion or molecule.
A symporter carries two different ions or
molecules, both in the same direction.
An antiporter carries two different ions or
molecules in different directions.
All of these transporters can transport small,
uncharged organic molecules such as glucose.
Proteins for Active Transport
Primary Active Transport
One of the most important
pumps in animals cells is
the sodium-potassium
pump (Na+-K+ ATPase),
which maintains the
electrochemical gradient
and the correct
concentrations of Na+ and
K+ in living cells. The
sodium-potassium pump
moves two K+ into the cell
while moving three Na+
out of the cell.
The sodium-potassium pump works in the following six steps:
– Three sodium ions bind to the protein.
– ATP is hydrolyzed by the protein carrier and a low-
energy phosphate group attaches to it.
– The carrier changes shape and opens towards the
exterior of the membrane. The three sodium ions are
released.
– Two potassium ions attach to the protein, causing the
low-energy phosphate group to detach.
– The carrier protein changes shape so that is open
towards the interior of the cell.
– The two potassium ions are released into the cytoplasm
and the process begins again.
Several things have happened as a result of this
process. First, there are now more sodium ions outside
of the cell than inside and more potassium ions inside
than out.
Second, since three sodium ions moved out for each
two potassium ions that moved in, the interior is
slightly more negative relative to the exterior.
This difference in charge is important in creating the
conditions necessary for secondary active transport.
The sodium-potassium pump is, therefore,
an electrogenic pump (a pump that creates a charge
imbalance), creating an electrical imbalance across the
membrane and contributing to the membrane potential.
Secondary Active Transport
(Co-transport)
Endocytosis
Endocytosis is a type of active transport that
moves particles, such as large molecules, parts of
cells, and even whole cells, into a cell. There are
different variations of endocytosis, but all share a
common characteristic.
The three types of endocytosis are phagocytosis,
pinocytosis, and receptor mediated
endocytosis.
Phagocytosis (“cell eating”) is the process by
which large particles, such as other cells or
relatively large particles, are taken in by a cell.
For example, when microorganisms invade the
human body, a type of white blood cell called a
neutrophil will “eat” the invaders through
phagocytosis, surrounding and engulfing the
microorganism, which is then destroyed by
lysosomes inside the neutrophil.
Through Pinocytosis (“cell drinking”), cells
take in molecules, including water, which the
cell needs from the extracellular fluid.
Pinocytosis results in a much smaller vesicle
than does phagocytosis, and the vesicle does
not need to merge with a lysosome.
Receptor-mediated endocytosis is a targeted
variation of endocytosis that employs receptor
proteins in the plasma membrane that have a
specific binding affinity for certain substances
Receptor-mediated
endocytosis, as in
phagocytosis, uses clathrin
protein attached to the
cytoplasmic side of the
plasma membrane. Some
human diseases are caused
by the failure of receptor-
mediated endocytosis.
Exocytosis
The reverse process of moving material into a cell is
the process of exocytosis. The purpose of exocytosis
is to expel material from the cell into the
extracellular fluid. Waste material is enveloped in
vesicle, which fuses with the interior of the plasma
membrane, expelling the waste material into the
extracellular space.
Cells also use exocytosis to secrete proteins such as
hormones, neurotransmitters, or parts of the extra
cellula rmatrix.
Methods of transport, energy requirements, and
types of material transported
Nerve Impulse Transmission
For the nervous system to function, neurons must
be able to send and receive signals. These signals
are possible because each neuron has a charged
cellular membrane (a voltage difference between
the inside and the outside), and the charge of this
membrane can change in response to
neurotransmitter molecules released from other
neurons and environmental stimuli.
Resting Membrane Potential
A neuron at rest is negatively charged: the inside
of a cell is approximately 70 millivolts more
negative than the outside (40−80 mV, note that
this number varies by neuron type and by
species). This voltage is called the resting
membrane potential; it is caused by differences
in the concentrations of ions inside and outside
the cell.
The difference in the number of positively charged
potassium ions (K+) inside and outside the cell
dominates the resting membrane potential.
The negative charge within the cell is created by the
cell membrane being more permeable to potassium
ion movement than sodium ion movement.
In neurons, potassium ions are maintained at high
concentrations within the cell while sodium ions are
maintained at high concentrations outside of the
cell.
As more cations are expelled from the cell than
taken in, the inside of the cell remains negatively
charged relative to the extracellular fluid.
Action Potential
A neuron can receive input from other neurons and,
if this input is strong enough, send the signal to
downstream neurons.
Transmission of a signal between neurons is
generally carried by a chemical called a
neurotransmitter.
Transmission of a signal within a neuron (from
dendrite to axon terminal) is carried by a brief
reversal of the resting membrane potential called an
action potential.
When neurotransmitter molecules bind to
receptors located on a neuron’s dendrites, ion
channels open. At excitatory synapses, this
opening allows positive ions to enter the neuron
and results in depolarization of the membrane a
decrease in the difference in voltage between the
inside and outside of the neuron.
A stimulus from a sensory cell or another neuron
depolarizes the target neuron to its threshold
potential (-55 mV). Na channels in the axon
hillock open, allowing positive ions to enter the
cell. Once the sodium channels open, the neuron
completely depolarizes to a membrane potential of
about +40 mV.
Action potentials are considered an "all-or
nothing" event, in that, once the threshold
potential is reached, the neuron always completely
depolarizes. Once depolarization is complete, the
cell must now "reset" its membrane voltage back
to the resting potential
Summary
Neurons have charged membranes because there are different
concentrations of ions inside and outside of the cell. Voltage-gated
ion channels control the movement of ions into and out of a neuron.
When a neuronal membrane is depolarized to at least the threshold
of excitation, an action potential is fired.
The action potential is then propagated along a myelinated axon to
the axon terminals. In a chemical synapse, the action potential
causes release of neurotransmitter molecules into the synaptic cleft.
Through binding to postsynaptic receptors, the neurotransmitter can
cause excitatory or inhibitory postsynaptic potentials by
depolarizing or hyperpolarizing, respectively, the postsynaptic
membrane.
In electrical synapses, the action potential is directly communicated
to the postsynaptic cell through gap junctions—large channel
proteins that connect the pre-and postsynaptic membranes.
Thank you
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Biochemistry of Cell Membrane.pptx

  • 1. MEMBRANE TRANSPORT Rajendra Dev Bhatt (PhD Scholar) Asst. Professor Clinical Biochemistry & Laboratory Medicine Fellow: Translational Research (2018-2022) in CVD in Nepal, NHLBI & NIH, USA
  • 2. The plasma membrane, which is also called the cell membrane, has many functions, but the most basic one is to define the borders of the cell and keep the cell functional. The plasma membrane is selectively permeable. This means that the membrane allows some materials to freely enter or leave the cell, while other materials cannot move freely, but require the use of a specialized structure, and occasionally, even energy investment for crossing. Introduction
  • 3. Membrane Components and Structure Among the most sophisticated functions of the plasma membrane is the ability to transmit signals by means of complex, integral proteins known as receptors. These proteins act both as receivers of extracellular inputs and as activators of intracellular processes. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors, and they activate intracellular response cascades when their effectors are bound.
  • 4. Fluid Mosaic Model The explanation proposed by Singer and Nicolson is called the fluid mosaic model. The model has evolved somewhat over time, but it still best accounts for the structure and functions of the plasma membrane as we now understand them. The fluid mosaic model describes the structure of the plasma membrane as a mosaic of components including phospholipids, cholesterol, proteins, and carbohydrates that gives the membrane a fluid character. Plasma membranes range from 5 to 10 nm in thickness.
  • 5. Components of a plasma membrane The principal components of a plasma membrane are lipids, proteins, and carbohydrates. The lipids include phospholipids and cholesterol Proteins. Carbohydrate chains are attached to the proteins and lipids on the outside surface of the membrane. Typical human cell, protein accounts for about 50% of the composition by mass, lipids account for about 40% of the composition by mass, with the remaining 10% of the com-position by mass being carbohydrates.
  • 6. The components and functions of the plasma membrane.
  • 7. Passive Transport Passive transport is a naturally occurring phenomenon and does not require the cell to exert any of its energy to accomplish the movement. In passive transport, substances move from an area of higher concentration to an area of lower concentration. A physical space in which there is a range of concentrations of a single substance is said to have a concentration gradient.
  • 8. Selective Permeability Recall that plasma membranes are amphipathic: They have hydrophilic and hydrophobic regions. This characteristic helps the movement of some materials through the membrane and hinders the movement of others. Lipid-soluble material with a low molecular weight can easily slip through the hydrophobic lipid core of the membrane. Substances such as the fat- soluble vitamins A, D, E, and K readily pass through the plasma membranes in the digestive tract and other tissues. Molecules of oxygen and carbon dioxide have no charge and so pass through membranes by simple diffusion.
  • 9. Diffusion • Diffusion is a passive process of transport. A single substance tends to move from an area of high concentration to an area of low concentration until the concentration is equal across a space.
  • 10. Facilitated diffusion In facilitated diffusion, materials diffuse across the plasma membrane with the help of membrane proteins. A concentration gradient exists that would allow these materials to diffuse into the cell without expending cellular energy. However, these materials are ions or polar molecules that are repelled by the hydrophobic parts of the cell membrane. Facilitated diffusion proteins shield these materials from the repulsive force of the membrane, allowing them to diffuse into the cell. These proteins are called transport-proteins and can be channels or carrier proteins.
  • 11. Channel proteins are trans-membrane proteins that fold in such as way as to form a channel or pore through the membrane. Each channel is specific for one particular substance.
  • 12. Some channel proteins are always open but many are “gated,” meaning that they can be opened and closed. If a channel is ligand-gated, the attachment of a particular molecule to the channel protein may cause it to open. Other channels are voltage-gated, requiring a change in voltage across the membrane to open them. Cells involved in the transmission of electrical impulses, such as nerve and muscle cells, have voltage-gated ion channels in their membranes.
  • 13. Another type of trans-membrane transporter protein is a carrier protein. Like channels, carrier proteins are usually specific for particular molecules. A carrier proteins binds a substance and, in doing so, triggers a change of its own shape, moving the bound molecule across the membrane.
  • 14. Osmosis Osmosis is the diffusion of water across a semipermeable membrane. Since it is diffusion, it depends on the concentration gradient, or the amount of water on each side of the membrane.
  • 15. Active transport Active transport mechanisms require the use of the cell’s energy, usually in the form of adenosine triphosphate (ATP). If a substance must move into the cell against its concentration gradient—that is, if the concentration of the substance inside the cell is greater than its concentration in the extracellular fluid (and vice versa)—the cell must use energy to move the substance. Some active transport mechanisms move small-molecular weight materials, such as ions, through the membrane. Other mechanisms transport much larger molecules.
  • 16. Electrochemical gradient The interior of living cells is electrically negative with respect to the extracellular fluid surrounding them. At the same time, cells have a lower concentration of (Na+) than does the extracellular fluid. Therefore, both the concentration gradient and the electrical gradient tend to drive Na+ into the cell. Conversely, cells have a higher concentration of K+ than the extracellular fluid does. Therefore, the concentration gradient tends to drive K+ out of the cell, while the electrical gradient tends to drive it inside the cell. The combined gradient of concentration and electrical charge that affects an ion is called its electrochemical gradient.
  • 17. Injection of a potassium solution into a person’s blood is lethal; this is used in capital punishment and euthanasia. Why do you think a potassium solution injection is lethal?
  • 18. Proteins for Active Transport The specific proteins that facilitate active transport are called transporters. There are three types of transporters. A uniporter carries one specific ion or molecule. A symporter carries two different ions or molecules, both in the same direction. An antiporter carries two different ions or molecules in different directions. All of these transporters can transport small, uncharged organic molecules such as glucose.
  • 19. Proteins for Active Transport
  • 20. Primary Active Transport One of the most important pumps in animals cells is the sodium-potassium pump (Na+-K+ ATPase), which maintains the electrochemical gradient and the correct concentrations of Na+ and K+ in living cells. The sodium-potassium pump moves two K+ into the cell while moving three Na+ out of the cell.
  • 21. The sodium-potassium pump works in the following six steps: – Three sodium ions bind to the protein. – ATP is hydrolyzed by the protein carrier and a low- energy phosphate group attaches to it. – The carrier changes shape and opens towards the exterior of the membrane. The three sodium ions are released. – Two potassium ions attach to the protein, causing the low-energy phosphate group to detach. – The carrier protein changes shape so that is open towards the interior of the cell. – The two potassium ions are released into the cytoplasm and the process begins again.
  • 22. Several things have happened as a result of this process. First, there are now more sodium ions outside of the cell than inside and more potassium ions inside than out. Second, since three sodium ions moved out for each two potassium ions that moved in, the interior is slightly more negative relative to the exterior. This difference in charge is important in creating the conditions necessary for secondary active transport. The sodium-potassium pump is, therefore, an electrogenic pump (a pump that creates a charge imbalance), creating an electrical imbalance across the membrane and contributing to the membrane potential.
  • 24. Endocytosis Endocytosis is a type of active transport that moves particles, such as large molecules, parts of cells, and even whole cells, into a cell. There are different variations of endocytosis, but all share a common characteristic. The three types of endocytosis are phagocytosis, pinocytosis, and receptor mediated endocytosis.
  • 25. Phagocytosis (“cell eating”) is the process by which large particles, such as other cells or relatively large particles, are taken in by a cell. For example, when microorganisms invade the human body, a type of white blood cell called a neutrophil will “eat” the invaders through phagocytosis, surrounding and engulfing the microorganism, which is then destroyed by lysosomes inside the neutrophil.
  • 26. Through Pinocytosis (“cell drinking”), cells take in molecules, including water, which the cell needs from the extracellular fluid. Pinocytosis results in a much smaller vesicle than does phagocytosis, and the vesicle does not need to merge with a lysosome. Receptor-mediated endocytosis is a targeted variation of endocytosis that employs receptor proteins in the plasma membrane that have a specific binding affinity for certain substances
  • 27. Receptor-mediated endocytosis, as in phagocytosis, uses clathrin protein attached to the cytoplasmic side of the plasma membrane. Some human diseases are caused by the failure of receptor- mediated endocytosis.
  • 28. Exocytosis The reverse process of moving material into a cell is the process of exocytosis. The purpose of exocytosis is to expel material from the cell into the extracellular fluid. Waste material is enveloped in vesicle, which fuses with the interior of the plasma membrane, expelling the waste material into the extracellular space. Cells also use exocytosis to secrete proteins such as hormones, neurotransmitters, or parts of the extra cellula rmatrix.
  • 29. Methods of transport, energy requirements, and types of material transported
  • 30. Nerve Impulse Transmission For the nervous system to function, neurons must be able to send and receive signals. These signals are possible because each neuron has a charged cellular membrane (a voltage difference between the inside and the outside), and the charge of this membrane can change in response to neurotransmitter molecules released from other neurons and environmental stimuli.
  • 31. Resting Membrane Potential A neuron at rest is negatively charged: the inside of a cell is approximately 70 millivolts more negative than the outside (40−80 mV, note that this number varies by neuron type and by species). This voltage is called the resting membrane potential; it is caused by differences in the concentrations of ions inside and outside the cell.
  • 32. The difference in the number of positively charged potassium ions (K+) inside and outside the cell dominates the resting membrane potential. The negative charge within the cell is created by the cell membrane being more permeable to potassium ion movement than sodium ion movement. In neurons, potassium ions are maintained at high concentrations within the cell while sodium ions are maintained at high concentrations outside of the cell. As more cations are expelled from the cell than taken in, the inside of the cell remains negatively charged relative to the extracellular fluid.
  • 33. Action Potential A neuron can receive input from other neurons and, if this input is strong enough, send the signal to downstream neurons. Transmission of a signal between neurons is generally carried by a chemical called a neurotransmitter. Transmission of a signal within a neuron (from dendrite to axon terminal) is carried by a brief reversal of the resting membrane potential called an action potential.
  • 34. When neurotransmitter molecules bind to receptors located on a neuron’s dendrites, ion channels open. At excitatory synapses, this opening allows positive ions to enter the neuron and results in depolarization of the membrane a decrease in the difference in voltage between the inside and outside of the neuron.
  • 35. A stimulus from a sensory cell or another neuron depolarizes the target neuron to its threshold potential (-55 mV). Na channels in the axon hillock open, allowing positive ions to enter the cell. Once the sodium channels open, the neuron completely depolarizes to a membrane potential of about +40 mV. Action potentials are considered an "all-or nothing" event, in that, once the threshold potential is reached, the neuron always completely depolarizes. Once depolarization is complete, the cell must now "reset" its membrane voltage back to the resting potential
  • 36. Summary Neurons have charged membranes because there are different concentrations of ions inside and outside of the cell. Voltage-gated ion channels control the movement of ions into and out of a neuron. When a neuronal membrane is depolarized to at least the threshold of excitation, an action potential is fired. The action potential is then propagated along a myelinated axon to the axon terminals. In a chemical synapse, the action potential causes release of neurotransmitter molecules into the synaptic cleft. Through binding to postsynaptic receptors, the neurotransmitter can cause excitatory or inhibitory postsynaptic potentials by depolarizing or hyperpolarizing, respectively, the postsynaptic membrane. In electrical synapses, the action potential is directly communicated to the postsynaptic cell through gap junctions—large channel proteins that connect the pre-and postsynaptic membranes.