LECTURE 1. PLASMA MEMBRANE.pptxhhjjjghfh

YOUDUBAGHA DINIPRE MCGREGOR B.
DEPARTMENT OF ANATOMY
Sunday, April 7, 2024 1
American International University
WEST AFRICA

A. STRUCTURE.
The plasma membrane is approximately 7.5 nm thick and consists
of two leaflets, known as the lipid bilayer that houses associated
integral and peripheral proteins.
1. The inner leaflet of the plasma membrane faces the cytoplasm,
and the outer leaflet faces the extracellular environment.
2. When examined by transmission electron microscopy (TEM), the
plasma membrane displays a trilaminar (unit membrane)
structure.
B. FUNCTION
1. The plasma membrane envelops the cell and maintains its
structural and functional integrity.
2. It acts as a semipermeable membrane between the cytoplasm and
the external environment.
3. It permits the cell to recognize macromolecules and other cells as
well as to be recognized by other cells.

4. It participates in the transduction of extracellular
signals into intracellular events.
5. It assists in controlling interaction between cells.
6. It maintains an electrical potential difference between
the cytoplasmic and extracellular sides.

A. The lipid bilayer is freely permeable to small, lipid-
soluble, nonpolar molecules but is impermeable to charged
ions.
1. Molecular structure. The lipid bilayer is composed of
phospholipids, glycolipids, and cholesterol, of which, in
most cells, phospholipids constitute the highest percentage.
a. Phospholipids are amphipathic molecules, consisting of one
polar (hydrophilic) head and two nonpolar (hydrophobic)
fatty acyl tails, one of which is usually unsaturated.
b. The two leaflets are not identical; instead the distribution of
the various types of phospholipids is asymmetrical.
(1) The polar head of each molecule faces the membrane
surface, whereas the tails project into the interior of the
membrane, facing each other.

(2) The tails of the two leaflets are mostly 16–18 carbon
chain fatty acids, and they form weak noncovalent
bonds that attach the two leaflets to each other.
c. Glycolipids are restricted to the extracellular aspect of
the outer leaflet. Polar carbohydrate residues of
glycolipids extend from the outer leaflet into the
extracellular space and form part of the glycocalyx.
d. Cholesterol, constituting 2% of plasmalemma lipids, is
present in both leaflets, and helps maintain the
structural integrity of the membrane.
e. Cholesterol and phospholipids can form
microdomains, known as lipid rafts, that can affect the
movement of integral proteins of the plasmalemma.

2. Fluidity of the lipid bilayer is crucial to exocytosis, endocytosis,
membrane trafficking, and membrane biogenesis.
a. Fluidity increases with increased temperature and with decreased
saturation of the fatty acyl tails.
b. Fluidity decreases with an increase in the membrane’s
cholesterol content.
B. Membrane proteins include integral proteins and peripheral
proteins and, in most cells, constitute approximately 50% of the
plasma membrane composition.
1. Integral proteins are dissolved in the lipid bilayer.
a. Transmembrane proteins span the entire thickness of the
plasma membrane and may function as membrane receptors,
enzymes, cell adhesion molecules, cell recognition proteins,
molecules that function in message transduction, and transport
proteins.
(1) Most transmembrane proteins are glycoproteins.
(2) Transmembrane proteins are amphipathic and contain
hydrophilic and hydrophobic amino acids, some of which
interact with the hydrocarbon tails of the membrane
phospholipids.

(3) Most transmembrane proteins are folded so that they
pass back and forth across the plasmalemma; therefore,
they are also known as multipass proteins.
b. Integral proteins may also be anchored to the inner (or
occasionally outer) leaflet via fatty acyl or prenyl groups.
c. In freeze-fracture preparations, integral proteins remain
preferentially attached to the P-face, the outer
(protoplasmic face) surface of the inner leaflet, rather than
the E-face (extracellular face).
2. Peripheral proteins do not extend into the lipid bilayer.
a. These proteins are located on the cytoplasmic aspect of
the inner leaflet.
b. The outer leaflets of some cells possess covalently linked
glycolipids to which peripheral proteins are anchored; these
peripheral proteins thus project into the extracellular space.
c. Peripheral proteins bind to the phospholipid polar groups
or integral proteins of the membrane via noncovalent
interactions.

d. They usually function as electron carriers (e.g.,
cytochrome c) part of the cytoskeleton or as part of an
intracellular second messenger system.
e. They include a group of anionic, calcium-dependent, lipid-
binding proteins known as annexins, which act to modify
the relationships of other peripheral proteins with the lipid
bilayer and also to function in membrane trafficking and the
formation of ion channels; synapsin I, which binds synaptic
vesicles to the cytoskeleton; and spectrin, which stabilizes
cell membranes of erythrocytes.
3. Functional characteristics of membrane proteins
a. The lipid-to-protein ratio (by weight) in plasma membranes
ranges from 1:1 in most cells to as much as 4:1 in myelin.
b. Some membrane proteins diffuse laterally in the lipid
bilayer; others are immobile and are held in place by
cytoskeletal components.

C. Glycocalyx (cell coat), located on the outer surface
of the outer leaflet of the plasmalemma, varies in
appearance (fuzziness) and thickness (up to 50 nm).
1. Composition. The glycocalyx consists of polar
oligosaccharide side chains linked covalently to most
proteins and some lipids (glycolipids) of the
plasmalemma. It also contains proteoglycans
(glycosaminoglycans bound to integral proteins).
2. Function
a. The glycocalyx aids in attachment of some cells (e.g.,
fibroblasts but not epithelial cells) to extracellular
matrix components.
b. It binds antigens and enzymes to the cell surface.
c. It facilitates cell-cell recognition and interaction.
d. It protects cells from injury by preventing contact with
inappropriate substances.

e. It assists T cells and antigen-presenting cells in
aligning with each other in the proper fashion and
aids in preventing inappropriate enzymatic
cleavage of receptors and ligands.
f. In blood vessels, it lines the endothelial surface to
decrease frictional forces as the blood rushes by
and it also diminishes loss of fluid from the vessel.

These processes include transport of a single molecule
(uniport) or cotransport of two different molecules in the
same (symport) or opposite (antiport) direction.
A. Passive transport includes simple and facilitated
diffusion. Neither of these processes requires energy
because molecules move across the plasma membrane
down a concentration or electrochemical gradient.
1. Simple diffusion transports small nonpolar molecules
(e.g., O2 and N2) and small, uncharged, polar molecules
(e.g., H2O, CO2, and glycerol). It exhibits little specificity,
and the diffusion rate is proportional to the concentration
gradient of the diffusing molecule.

2. Facilitated diffusion occurs via ion channels and/or
carrier proteins, structures that exhibit specificity for
the transported molecules.
 Not only is it faster than simple diffusion but it is also
responsible for providing a pathway for ions and large polar
molecules to traverse membranes that would otherwise be
impermeable to them.
a. Ion channel proteins are multipass transmembrane
proteins that form small aqueous pores across membranes
through which specific small water-soluble molecules and
ions pass down an electrochemical gradient (passive
transport).
b. Aquaporins are channels designed for the rapid
transport of water across the cell membrane without
permitting an accompanying flow of protons to pass
through the channels.

 They accomplish this by forcing the water molecules to
flip-flop halfway down the channel, so that water
molecules enter aquaporins with their oxygen leading
into the channel and leave with their oxygen trailing the
hydrogen atoms.
c. Carrier proteins are multipass transmembrane
proteins that undergo reversible conformational
changes to transport specific molecules across the
membrane; these proteins function in both passive
transport and active transport.

Cystinuria is a hereditary condition caused by
abnormal carrier proteins that are unable to remove
cystine from the urine, resulting in the formation of
kidney stones.

B. Active transport is an energy-requiring process
that transports a molecule against an
electrochemical gradient via carrier proteins.
1. Na–K pump
a. Mechanism.
The Na–K pump involves the antiport transport of Na
and K ions mediated by the carrier protein, Na–K
adenosine triphosphatase (ATPase).
(1) Three Na ions are pumped out of the cell and two
K ions are pumped into the cell.
(2) The hydrolysis of a single ATP molecule by the
Na–K ATPase is required to transport five ions.

b. Function
(1) The primary function is to maintain constant cell volume by
decreasing the intracellular ion concentration (and thus the
osmotic pressure) and increasing the extracellular ion
concentration, thus decreasing the flow of water into the cell.
(2) The Na–K pump also plays a minor role in the maintenance
of a potential difference across the plasma membrane.
2. Glucose transport involves the symport movement of glucose
across an epithelium (transepithelial transport). Transport is
frequently powered by an electrochemical Na gradient, which
drives carrier proteins located at specific regions of the cell
surface.
3. ATP-Binding Cassette transporters (ABC-transporters) are
transmembrane proteins that have two domains, the
intracellularly facing nucleotide-binding domain (ATP binding
domain) and the membrane-spanning domain
(transmembrane domain).

In eukaryotes, ABCtransporters function in exporting
materials, such as toxins and drugs, from the cytoplasm
into the extracellular space, using ATP as an energy
source.
 ABC-transporters may have additional functions, such
as those of the placenta, which presumably protect the
developing fetus from xenobiotics, macromolecules
such as antibiotics, not manufactured by cells of the
mother.

 Multidrug-resistant proteins (MDR proteins) are
ABC-transporters that are present in certain cancer
cells that are able to transport the cytotoxic drugs
administered to treat the malignancy.
 It has been shown that in more than one-third of the
cancer patients, the malignant cells develop MDR
proteins that interfere with the treatment modality
being used.

C. Facilitated diffusion of ions can occur via ion channel
proteins or ionophores.
1. Selective ion channel proteins permit only certain ions
to traverse them.
a. K leak channels are the most common ion channels.
These channels are ungated and leak K, the ions most
responsible for establishing a potential difference across the
plasmalemma.
b. Gated ion channels open only transiently in response to
various stimuli. They include the following types:
(1) Voltage-gated channels open when the potential
difference across the membrane changes (e.g., voltage-
gated Na channels, which function in the generation of
action potentials).
(2) Mechanically gated channels open in response to a
mechanical stimulus (e.g., the tactile response of the hair
cells in the inner ear).

(3) Ligand-gated channels open in response to the
binding of a signaling molecule or ion. These
channels include neurotransmitter-gated channels,
nucleotide-gated channels, and G protein–gated K
channels of cardiac muscle cells.

Ligand-gated ions channels are probably the location
where anesthetic agents act to block the spread of
action potentials.

2. Ionophores are lipid-miscible molecules that form a
complex with ions and insert into the lipid bilayer to
transport those ions across the membrane. There are
two ways in which they perform this function:
a. They enfold the ion and pass through the lipid
bilayer.
b. They insert into the cell membrane to form an ion
channel whose lumen is hydrophilic.
 Ionophores are frequently fed to cattle and poultry as
antibiotic agents and growth enhancing substances.

A. Signaling molecules, secreted by signaling cells, bind to
receptor molecules of target cells, and in this fashion, these
molecules function in cell-to-cell communication in order to
coordinate cellular activities.
 Examples of such signaling molecules that effect
communications include neurotransmitters, which are released
into the synaptic cleft, endocrine hormones, which are carried in
the bloodstream and act on distant target cells; and hormones
released into the intercellular space, which act on nearby cells
(paracrine hormones) or on the releasing cell itself (autocrine
hormones).
1. Lipid-soluble signaling molecules penetrate the plasma
membrane and bind to receptors within the cytoplasm or
inside the nucleus, activating intracellular messengers.
Examples include hormones that influence gene transcription.

2. Hydrophilic signaling molecules bind to and activate
cell-surface receptors (as do some lipid-soluble signaling
molecules) and have diverse physiologic effects.
Examples include neurotransmitters and numerous hormones
(e.g., serotonin, thyroid stimulating hormone, insulin).
B. Membrane receptors are primarily integral membrane
glycoproteins. They are embedded in the lipid bilayer and
have three domains, an extracellular domain that
protrudes into the extracellular space and has binding sites
for the signaling molecule, a transmembrane domain that
passes through the lipid bilayer, and an intracellular
domain that is located on the cytoplasmic aspect of the
lipid bilayer and contacts either peripheral proteins or
cellular organelles, thereby transducing the extracellular
contact into an intracellular event.

1. Function
a. Membrane receptors control plasmalemma
permeability by regulating the conformation of ion
channel proteins.
b. They regulate the entry of molecules into the cell (e.g.,
the delivery of cholesterol via low-density lipoprotein
receptors).
c. They bind extracellular matrix molecules to the
cytoskeleton via integrins, which are essential for cell-
matrix interactions.
d. They act as transducers to translate extracellular events
into an intracellular response via the second messenger
systems.
e. They permit pathogens that mimic normal ligands to
enter cells.
2. Types of membrane receptors
a. Channel-linked receptors bind a signaling molecule that
temporarily opens or closes the gate, permitting or
inhibiting the movement of ions across the cell membrane.
Examples include nicotinic acetylcholine receptors on the

b. Catalytic receptors are single-pass transmembrane
proteins.
(1) Their extracellular moiety is a receptor and their
cytoplasmic component is a protein kinase.
(2) Some catalytic receptors lack an extracytoplasmic
moiety and as a result are continuously activated;
such defective receptors are coded for by some
oncogenes.
(3) Examples of catalytic receptors include the
following:
(a) Insulin, which binds to its receptor, which
autophosphorylates. The cell then takes up the
insulin-receptor complex by endocytosis, enabling the
complex to function within the cell.

(b) Growth factors (e.g., epidermal growth factor, platelet-derived
growth factor) bind to specific catalytic receptors and induce mitosis.
c. G protein–linked receptors are transmembrane proteins associated
with an ion channel or with an enzyme that is bound to the
cytoplasmic surface of the cell membrane.
(1) These receptors interact with heterotrimeric G protein (guanosine
triphosphate [GTP]-binding regulatory protein) after binding of a
signaling molecule. The heterotrimeric G protein is composed of three
subunits: alpha, beta and gamma complex. The binding of the
signaling molecule causes either
(a) the dissociation of the alpha subunit from the beta and gamma
complex where the subunit interacts with its target or
(b) the three subunits do not dissociate, but either the alpha subunit
and/or the beta and gamma complex become activated and can
interact with their targets.
This interaction results in the activation of intracellular second
messengers, the most common of which are cyclic adenosine
monophosphate (cAMP), Ca2, and the inositol phospholipid–
signaling pathway.

(2) Examples include the following:
(a) Heterotrimeric G proteins, which are folded in such a
fashion that they make seven passes as they penetrate the cell
membrane. These are stimulatory G protein (Gs), inhibitory G
protein (Gi), phospholipase C activator G protein (Gq),
olfactory-specific G protein (Golf), transducin (Gt), Go which
acts to open K channels and closes Ca2 channels, and G12/13
which controls the formation of the actin component of the
cytoskeleton and facilitates migration of the cell.
(b) Monomeric G proteins (low-molecular-weight G proteins)
are small single-chain proteins that also function in signal
transduction.
1. Various subtypes resemble Ras, Rho, Rab, and ARF proteins.
2. These proteins are involved in pathways that regulate cell
proliferation and differentiation, protein synthesis, attachment
of cells to the extracellular matrix, exocytosis, and vesicular
traffic.

 Venoms, such as those of some poisonous snakes,
inactivate acetylcholine receptors of skeletal muscle
sarcolemma at neuromuscular junctions.
 Autoimmune diseases may lead to the production of
antibodies that specifically bind to and activate certain
plasma membrane receptors. An example is Graves
disease (hyperthyroidism)

Cholera toxin is an exotoxin produced by the
bacterium Vibrio cholerae that alters Gs protein so
that it is unable to hydrolyze its GTP molecule. As a
result, cAMP levels increase in the surface-absorptive
cells of the intestine, leading to excessive loss of
electrolytes and water and severe diarrhea.
Pertussis toxin, the product of the bacterium that
causes whooping cough, inserts ADP-ribose into the
subunits of trimeric G proteins, causing the
accumulation of the inactive form of G proteins
resulting in irritation of the mucosa of the bronchial
passages.
Defective Gs proteins may lead to mental retardation,
diminished growth and sexual development, and
decreased responses to certain hormones.

The plasmalemma and cytoskeleton associate through integrins.
The extracellular domain of integrins binds to extracellular
matrix components, and the intracellular domain binds to
cytoskeletal components. Integrins stabilize the plasmalemma
and determine and maintain cell shape.
A. Red blood cells have integrins, called band 3 proteins, which
are located in the plasmalemma. The cytoskeleton of a red
blood cell consists mainly of spectrin, actin, band 4.1 protein,
and ankyrin.
1. Spectrin is a long, flexible protein (about 110 nm long),
composed of an alpha chain and a beta chain, that forms
tetramers and provides a scaffold for structural
reinforcement.
2. Actin attaches to binding sites on the spectrin tetramers and
holds them together, thus aiding in the formation of a
hexagonal spectrin latticework.

3. Band 4.1 protein binds to and stabilizes spectrin–
actin complexes.
4. Ankyrin is linked to both band 3 proteins and
spectrin tetramers, thus attaching the spectrin–actin
complex to transmembrane proteins.
B. The cytoskeleton of nonerythroid cells consists of
the following major components:
1. Actin (and perhaps fodrin), which serves as a
nonerythroid spectrin.
2. Alpha Actinin, which cross-links actin filaments to
form a meshwork.
3. Vinculin, which binds to alpha actinin and to
another protein, called talin, which, in turn, attaches
to the integrin in the plasma membrane.

1. Hereditary spherocytosis results from a defective
spectrin that has a decreased ability to bind to band 4.1
protein. The disease is characterized by fragile, misshapen
red blood cells, or spherocytes; destruction of these
spherocytes in the spleen leads to anemia.
2. During high-speed car accidents and often in shaken
baby syndrome, the sudden accelerating and decelerating
forces applied to the brain cause shearing damage to axons,
especially at the interface between white matter and gray
matter. The stretching of the axons result in diffuse axonal
injury, a widespread lesion whose consequence is the
onset of a persistent coma from which only 10% of the
affected individuals regain consciousness.

Examination of the affected tissue displays irreparable
cleavage of spectrin, with an ensuing destruction of
the neuronal cytoskeleton leading to loss of plasma
membrane integrity and eventual cell death.

LECTURE 1. PLASMA MEMBRANE.pptxhhjjjghfh

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