CELL

PHYSIOLOGY
Associate Professor
DR IMRAN AFTAB
Lysosomes
• Lyso; dissolving and somes; bodies. They are formed from golgi
complex.
• ~ 60 digestive & hydrolytic enzymes.
• pH 5, lysosomal membrane has active transport pumps that
import H+ ions.
• Digest substances that enter a cell via endocytosis and transport
final products of digestion into cytosol.
• Carry out autophagy, the digestion of worn-out organelles.
• Carry out autolysis, the digestion of entire cell.
• Carry out extracellular digestion.
Lysosomes
Clinical Connection: LYSOSOMAL STORAGE
DISEASES
•Some disorders are caused by faulty or absent lysosomal enzymes.
•Tay-Sachs disease, most often affects children of eastern European
Jewish descent, is an inherited condition characterized by the
absence of a single lysosomal enzyme called Hex A.
•This enzyme normally breaks down a membrane glycolipid called
ganglioside GM2 that is especially prevalent in nerve cells.
• As the excess ganglioside GM2 accumulates, the nerve cells
function less efficiently.
•Children with Tay-Sachs disease typically experience seizures and
muscle rigidity.
•They gradually become blind, demented, uncoordinated and usually
die before the age of 5.
Peroxisomes
• Peroxi; peroxide and somes; bodies are small bodies or
microbodies.
•Contain several oxidases, that can oxidize (remove hydrogen
atoms from) various organic substances e.g. amino acids and fatty
acids are oxidized in peroxisomes as part of normal metabolism.
•Oxidize toxic substances, such as alcohol (abundant in the liver).
•Byproduct of the oxidation reactions is H2O2, a potentially toxic
compound. enzyme catalase, which decomposes H2O2.
Non-membrane bound organelles
• Ribosomes
• Cytoskeleton
• Centrosome
Ribosomes
•Somes; bodies.
•High content of one type
of nucleic acid; ribosomal
•RNA (rRNA).
•Structurally; 2 subunits
and synthesized in nucleus
and assembled in
cytoplasm.
•Synthesis of protein.
Cytoskeleton
• Microfilaments
• Intermediate filaments
• Microtubules

Microfilament
• Thinnest elements of the cytoskeleton.
• They are composed of the protein actin and are
prevalent at the edges of the cell.
• They help generate movement (muscle contraction,
cell division and cell locomotion) and provide
mechanical support (basic strength and
shapes of cells).
Intermediate filaments
••These are thicker than microfilaments but thinner than
microtubules.
•• Several different proteins can compose intermediate filaments,
which are exceptionally strong.
•They are found in parts of cells subject to mechanical stress, help
stabilize the position of organelles such as the nucleus and help
attach cells to one another
Microtubules
•• These are the largest of the cytoskeletal components and are
long, un-branched hollow tubes composed mainly of the protein
tubulin.
•Assembly of microtubules begins in an organelle called the
centrosome.
•The microtubules grow outward from the centrosome toward
the periphery of the cell.
•Help determining cell shape.
•They also function in the movement of organelles such as
secretory vesicles, of chromosomes during cell division and of
specialized cell projections, such as cilia and flagella.
Cilia & Flagella
• Cilia: (eyelashes) are numerous, short, hair-like
projections that extend from the surface of the cell.
• Flagella: (whip) is long and moves entire cell.
• Each cilium contains a core of 20 microtubules surrounded by
plasma membrane.
• The microtubules are arranged such that one pair in the center
is surrounded by nine clusters of two fused microtubules
(doublets).
• Each cilium is anchored to a basal body just below the surface
of the plasma membrane.
Centrosome
•Located near the nucleus & consists of two components: a pair
of centrioles and peri-centriolar material.
•Two centrioles are cylindrical structures, each composed of
nine clusters of three microtubules arranged in a circular pattern.
•The long axis of one centriole is at a right angle to the long axis
of the other.
•Surrounding the centrioles is peri-centriolar material which
contains hundreds of ring-shaped complexes composed of the
protein tubulin.
•These tubulin complexes are the organizing centers for growth
of the mitotic spindle, which plays a critical role in cell division
and for microtubule formation in non-dividing cells.
CELL
PHYSIOLOGY
DR IMRAN AFTAB
 Types of Cell Junctions
Contact points between the plasma membrane of tissue
cells.

 Tight Junctions

 Desmosomes

 Gap Junctions

 Hemi-desmosomes

 Adherence
Tight Junctions
 Transmembrane Proteins of opposite cells attach in a
tight zipper-like fashion
 No leakage
 E.g. stomach, intestine, kidneys, epithelium of skin to
retard the passage of substances
between cells and prevent the
contents of these organs from leaking
into the blood or surrounding tissues.
Tight Junctions
Adherens Junctions
contain plaque, a dense layer of proteins on the inside of the
plasma membrane that attaches both to membrane proteins and
microfilaments of the cytoskeleton. Transmembrane
glycoproteins called cadherins join the cells. Each cadherin
inserts into the plaque from the opposite side of the plasma
membrane, partially crosses the intercellular space (the space
between the cells) and connects to cadherins of an adjacent
cell.
In epithelial cells, adherens junctions often form adhesion
belts because they encircle the cell similar to the way a belt
encircles your waist.
Adherens junctions help epithelial surfaces resist separation
during various contractile activities, as when food moves
through the intestines.
Desmosomes (desmo;bands)
 Cytoplasmic plaques of two cells bind with the aid of
intermediate filaments of keratin
 Allows for stretching
 E.g. Stomach, Bladder, Heart
Hemidesmosomes
Resemble desmosomes but they do not link adjacent
cells. The name arises from the fact that they look like half
of a desmosome.
The transmembrane glycoproteins in hemidesmosomes
are integrins rather than cadherins.
 On the inside of the plasma membrane, integrins
attach to intermediate filaments made of the protein
keratin.
 On the outside of the plasma membrane, the integrins
attach to the protein laminin, which is present in the
basement membrane.
 Thus, hemidesmosomes anchor cells not to each other
but to the basement membrane.
Gap

Junctions
Channel proteins (connexons) of
opposite cells join together providing
channels for ions, sugars, amino acids,
and other small molecules to pass.
 Allows communication between cells.

 E.g. Heart muscle, animal embryos,

transfer of nutrients and perhaps

wastes, takes place
through gap junctions in avascular
tissues such as the lens and cornea of
the eye.
Gap Junctions
Importance of cell membrane
 Ion channels, pores or holes through which specific

ions, such as potassium ions (K), can flow to get into

or out of the cell. Most ion channels are selective;
they allow only a single type of ion to pass through.
 Act as carriers, selectively moving a polar substance

or ion from one side of the membrane to the other.

Carriers are also known as transporters.
 Receptors serve as cellular recognition sites. Each

type of receptor recognizes and binds a specific type

of molecule. For instance, insulin receptors bind the
hormone insulin.
 Enzymes that catalyze specific chemical reactions at
the inside or outside surface of the cell.
 Linkers, which anchor proteins in the plasma
membranes of neighboring cells to one another or to
protein filaments inside and outside the cell.
 Membrane glycoproteins and glycolipids often serve
as cell identity markers. They may enable a cell to
recognize other cells of the same kind during tissue
formation or to recognize and respond to potentially
dangerous foreign cells. The ABO blood type
markers are one example of cell identity markers.
When you receive a blood transfusion, the blood type
must be compatible with your own.
CELL
PHYSIOLOGY
DR IMRAN AFTAB
Movement Across Membranes
 Membranes permeability
• Permeability depends on the interaction of a molecule with the
hydrophobic core of the membrane.
• Hydrophobic molecules, can dissolve in the lipid bilayer and cross
easily
• hydrocarbons
• CO2
• O2
• Ions and polar molecules pass through with difficulty.
• small molecules, like water, and larger critical molecules, like
glucose and other sugars.
• Ions, whether atoms or molecules, also have difficulties penetrating
the hydrophobic core.
• Proteins can assist and regulate the transport of ions and polar
molecules.
 Traffic Across Membranes
• Passive Transport is • Active Transport is the
diffusion across a pumping of solutes
membrane against their gradients
• Osmosis is the passive • Sodium-Potassium
transport of water pump
• Cell survival depends • Co transport
on balancing water • Exocytosis,
uptake and loss Endocytosis, and
• Facilitated Diffusion Pinocytosis
Gradient across membrane
A concentration gradient is a difference in the
concentration of a chemical from one place to another,
such as from the inside to the outside of the plasma
membrane.

For instance, oxygen molecules and Na ions are more

concentrated in the extracellular fluid than in the cytosol;
the opposite is true of carbon dioxide molecules and K
ions.
 The plasma membrane creates a difference in the
distribution of positively and negatively charged ions
between the two sides of the plasma membrane.

 Typically, the inner surface of the plasma

membrane is more negatively charged and the outer
surface is more positively charged. A difference in
electrical charges between two regions constitutes an
electrical gradient.

 It occurs across the plasma membrane, this charge

difference is termed the membrane potential.
Transport across plasma membrane
• Passage across the membrane is either passive or
active
• Passive transport requires no ATP
• movement down concentration gradient
• facilitated and simple diffusion
• Active transport requires ATP
• movement against concentration gradient
• carrier mediated
• vesicular transport
Membrane proteins in transfer of molecules
Two main classes of membrane proteins that mediate
the transfer:
Carrier proteins (also called carriers, permeases, or
transporters); which have moving parts to shift
specific molecules across the membrane.

Channel proteins; which form a narrow hydrophilic

pore, allowing the passive movement of small
inorganic ions.
 Types of Transport Processes
 Diffusion; results from random motion of particles
(ions, molecules) is a passive process.

 Carrier-mediated transport; requires the presence

of specialized integral proteins, can be passive or
active.

 Vesicular transport; Movement of materials with

small membranous sacs, or vesicles, always an active
process.
 Tool to increase the permeability of the
specific ions
•Ionophores are small hydrophobic molecules that
dissolve in lipid bilayers and increase their
permeability to specific inorganic ions.

•Most are synthesized by microorganisms.

•They are widely used as tools to increase the ion

permeability of membranes in studies on synthetic
bilayers, cells, or cell organelles.
• There are two classes of ionophores - mobile ion
carriers and channel formers.
 Diffusion through lipid bilayer
• Nonpolar, hydrophobic substances diffuse through
lipid layer; these are “lipid soluble” or lipophilic
(fat-loving) substances.

 Diffusion through channel proteins

• Water and charged hydrophilic solutes diffuse
through channel proteins; these are lipid insoluble or
lipophobic (fat fearing) substances.
 Cells control permeability by regulating number of
channel proteins.
 Simple Diffusion
 Net movement of particles from area of high
concentration to area of low concentration.
 Due to their constant and random motion.
 Difference between the high and low concentrations is
a concentration gradient.
 Diffusion tends to eliminate the gradient.
Examples:
 Scent of fresh flowers, drop of ink coloring a glass of
water, movement of oxygen and CO2 through cell
membranes.
Simple diffusion – nonpolar and lipid-soluble substances.
Diffuse directly through the lipid bilayer
Diffuse through channel proteins
Lipophilic substances can enter cells easily because they
diffuse through the lipid portion of the membrane
Examples are fatty acids, steroids, alcohol, oxygen,
carbon dioxide, and urea
Factors that Influence Diffusion Rates
 Distance -
 The shorter the distance, the more quickly gradients are
eliminated
 Few cells are farther than 125 microns from a blood
vessel
 Pneumonia, fluid collects in the lungs; the additional fluid
increases the diffusion distance because oxygen must move
through both the built-up fluid and the membrane to reach the
bloodstream.
 Molecular Size
 Ions and small molecules diffuse more rapidly
Factors that Influence Diffusion Rates
 Temperature -
  temp.,  motion of particles
 Body’s diffusion processes occur rapidly in a person with a
fever.
 Steepness of concentrated gradient -
 The larger the gradient, the faster diffusion proceeds
 Membrane surface area -
 The larger the area, the faster diffusion proceed
 lung diseases, such as emphysema, reduce the surface area.
This slows the rate of oxygen diffusion and makes breathing
more difficult.
Facilitated

Diffusion
Channel-Mediated Diffusion
 Membrane channels are transmembrane proteins
 Only 0.8 nm in diameter
 Used by ions, very small water-soluble compounds
 Much more complex than simple diffusion
 Size and charge of the ion affects which channels it
can pass through
 CARRIER-MEDIATED FACILITATED
DIFFUSION
 a carrier (also called a transporter)
 Used to move a solute down its concentration gradient
across the plasma membrane.
 Solute binds to a specific carrier on one side of the
membrane and is released on the other side after the
carrier undergoes a change in shape.
 Substances that move across the plasma membrane by
carrier mediated facilitated diffusion include glucose,
fructose, galactose, and some vitamins.
Glucose enters many body cells by carrier-mediated
facilitated diffusion as follows;
•Glucose binds to a specific type of carrier protein called
the glucose transporter (GluT) on the outside surface of
the membrane.
•As the transporter undergoes a change in shape, glucose
passes through the membrane.
•The transporter releases glucose on the other side of the
membrane.
Diffusion Through the Plasma Membrane
 Osmosis: A Special Case of Diffusion
 Each solute in the intra- and extracellular fluids diffuses
as if it were the only material in solution.
 From more to less, i.e. down the concentration gradient
 Some into the cytosol, others out of the cytosol
 Yet, total concentration of ions and molecules on either
side of the membrane stays the same
 This equilibrium persists because a typical cell
membrane is freely permeable to water.
 Whenever a solute concentration gradient exist, a
concentration gradient for water also exists.
 Thus, the higher the solute concentration, the lower the
water concentration.
 Osmosis - By Definition
 Movement of water
 Across a selectively permeable membrane

 Down its concentration gradient (from high to low

concentration)
 Toward the solution containing the higher solute
concentration.
Continues until water concentrations and solute
concentrations are the same on either side of the
membrane
 Two ways: (1) by moving through the lipid bilayer via

simple diffusion, as previously described earlier. (2) by

moving through aquaporins, integral membrane
proteins that function as water channels.
Osmosis & Cells
 Important because large volume changes caused by
water movement disrupt normal cell function
 Cell shrinkage or swelling
• Isotonic: cell neither shrinks nor swells
• Hypertonic: cell shrinks (crenation)
• Hypotonic: cell swells (lysis)
Effects of Tonicity on RBCs

Hypotonic, isotonic and hypertonic solutions affect the fluid

volume of a red blood cell. Notice the crenated and swollen
cells.
Filtration
 Cell membrane works like a sieve
 Depends on pressure difference on either side of a
partition
 Moves from side of greater pressure to lower
 Water and small molecules move through the pores of
the membrane while large molecules don’t.
 Example: urine formation in the kidneys.
Membrane Carriers

Uniporter
 carries only one solute at a time

Symport
 carries 2 or more solutes simultaneously in same
direction (cotransport)

Antiport
 carries 2 or more solutes in opposite directions
(counter transport)
sodium-potassium pump brings in K+ and
removes Na+ from cell

Any carrier type can use either facilitated diffusion or
active transport
 Saturation of a Carrier Protein
1. When the concentration of x molecules outside the
cell is low, the transport rate is low because it is limited
by the number of molecules available to be transported.

2. When more molecules are present outside the cell, as

long as enough carrier proteins are available, more
molecules can be transported; thus, the transport rate
increases.
3. The transport rate is limited by the number of
carrier proteins and the rate at which each carrier
protein can transport solutes. When the number of
molecules outside the cell is so large that the carrier
proteins are all occupied, the system is saturated and
the transport rate cannot increase.
Saturation of a Carrier Protein
 Active Transport
 Uses ATP to move solutes across a membrane
 It is not dependent on a concentration gradient
 Can move substances against their concentration
gradients - i.e. from lower to higher concentrations.
 Allows for greater accumulation of a substance on one
side of the membrane than on the other.
 Carrier proteins utilized called ion or exchange pumps.
 Ion pumps: actively transport Na+, K+, Ca++, Cl-
 Exchange pumps: Na+-K+ pump
 Types of Active Transport
 Primary active transport; (transport of solute
against its concentration gradient, coupled directly
to an exergonic chemical reaction, e.g., ATP
hydrolysis).
 Secondary active transport; (energy from ATP
hydrolysis is used to generate a gradient of another
solute, and the transport of that solute "down" its
concentration gradient is used to drive transport of
a different solute against its concentration
gradient)
Types of Active Transport
Types of Active Transport
Sodium-Potassium Pump
K+ is released and Na+ sites 1
are ready to bind Na+ again; Extracellular fluid Binding of cytoplasmic Na+ to the pump protein
the cycle repeats. stimulates phosphorylation by ATP.

Cytoplasm

2
Phosphorylation causes the
protein to change its shape.

Concentration gradients of
K+ and Na+

3
5
The shape change expels Na+ to the
Loss of phosphate restores the
outside, and extracellular K+ binds.
original conformation of the pump
protein. 4

K+ binding triggers release of the

phosphate group.
Functions of Na+ -K+ Pump
 Regulation of cell volume
 “fixed anions” attract cations causing osmosis
 cell swelling stimulates the Na+- K+ pump to
 ion concentration,  osmolarity and cell swelling
 Maintenance of a membrane potential in all cells
 pump keeps inside negative, outside positive
 Secondary active transport (ATP used not directly)
 steep concentration gradient of Na+ and K+
maintained across the cell membrane
 carriers move Na+ with 2nd solute easily into cell
 SGLT saves glucose in kidney
 Secondary Active Transport

Ions or molecules move in same (symport) or
different (antiport) direction.

Co-transport of Na+ and glucose.

 A sodium-potassium exchange pump maintains a

concentration of Na that is higher outside the cell
than inside. Active transport.

 Na moves back into the cell by a carrier protein

that also moves glucose. The concentration
gradient for Na provides the energy required to
move glucose against its concentration gradient.
Secondary Active Transport
Vesicular Transport
 Transport large particles or fluid droplets through
membrane in vesicles uses ATP
 Exocytosis –transport out of cell
 Endocytosis –transport into cell
 Phagocytosis – engulfing large particles
 Pinocytosis – taking in fluid droplets
 Receptor mediated endocytosis – taking in
specific molecules bound to receptors
 Endocytosis

 Packaging of extracellular materials in vesicles at the

cell surface.
 Involves relatively large volumes of extracellular
material.
 Requires energy in the form of ATP.
 Three major types
 Receptor-mediated endocytosis

 Pinocytosis

 Phagocytosis
Receptor Mediated Endocytosis
 A selective process, take up specific ligands.
 Involves formation of vesicles at surface of membrane
 Vesicles contain receptors on their membrane
 Vesicles contain specific target molecule in high
concentration.
 cells take up cholesterol containing low-density
lipoproteins (LDLs), transferrin (an iron-transporting
protein in the blood), some vitamins, antibodies and
certain hormones by receptor-mediated endocytosis.
Clathrin-coated vesicle in


cytoplasm

 uptake of LDL from

bloodstream
 If receptors are lacking,
LDL’s accumulate and
hypercholesterolemia
develops
 Human immunodeficiency
virus (HIV), causes AIDS,
attach to a receptor called CD4
(plasma membrane of white
blood cells called helper T
cells). Binding to CD4, HIV
enters the helper T cell via
receptor-mediated
endocytosis.
Receptor Mediated Endocytosis
Caveolin forces inward curvature in
membranes.
Bulk-phase endocytosis or Pinocytosis
(Cell-Drinking)
 Taking in droplets of ECF occurs in all
human cells, especially absorptive cells in
the intestines and kidneys.

 Not as selective as ‘receptor-mediated

endocytosis’
 Membrane caves in, then pinches off into
the cytoplasm as pinocytotic vesicle.

 No receptors are involved.

Pinocytosis
Phagocytosis
Vesicular Transport: Exocytosis
 Secreting material by secretary cells or replacement
of plasma membrane or occurs in nerve cells.