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CELL PHYSIOLOGY

CELLULAR PHYSIOLOGY
The word “cell” means “a small chamber”.
Human body is composed of trillions of cells,
each a microscopic compartment.

The cell is the structural and functional unit of


life. Bounded by a cell membrane, which
maintains the homeostasis of the cell interior.
An overview of cell structure
A typical cell, as seen by light microscope consists of
Cell membrane/ plasma membrane (encloses the cells)
Cytoplasm (portion of the cell’s interior not occupied by nucleus)
Nucleus (contains the cell’s genetic material)
Cell Theory according to Schwann 1839

1) Cell is the unit of structure, physiology, and


organization in living things.

2) Cell retains a dual existence as a distinct entity


and a building block in the construction of
organisms.
Rudolph Virchow's
powerful dictum (1855), "Omnis cellulae
cellula"...

The modern tenets of the Cell Theory include:

1. All known living things are made up of cells.


2. The cell is structural & functional unit of all living things.
3. All cells come from pre-existing cells by division.
(Spontaneous Generation does not occur).
4. Cells contains hereditary information which is passed from
cell to cell during cell division.
5. All cells are basically the same in chemical composition.
6. All energy flow (metabolism & biochemistry) of life occurs
within cells.
Cell membrane
• Forms a dynamic interface between the
intracellular and extracellular environments.

• It serves the following functions:


– The maintenance of cell shape and structure
– A transport function
– Intercellular communication
– Intercellular adhesion
Structure of cell membrane (organization of phospholipid
& proteins molecule in a lipid bilayer)
The thickness of cell membranes ranges from 6–10 nm, typically
being about 7.5 nm. Cell membranes are composed primarily of
lipids and proteins.
• Lipids are phospholipids,sphingomyelin, & cholesterol.

• Membrane lipids form self-sealing bilayers. They are


amphipathic molecules, with hydrophobic (core) and hydrophilic
moieties (lines both surfaces).
• Phospholipid bilayer (approximately 47%)

– Forms basic structure of cell that form fence around the cell.

– Its hydrophobic interior serves a barrier to passage of water-


soluble substances between the ICF & ECF.

– Maintains fluidity of membrane.

On electron microscopy, trilaminar structure


•Proteins (approximately 50%)
1.Peripheral proteins
Are present peripheral to the lipid
bilayer both inside & outside to it.
– Intrinsic proteins
– Extrinsic or surface proteins

2. Integral or Transmembrane proteins

Extend into the lipid bilayer


Functions:
• Channel protein
• Carrier proteins
• Receptor proteins
• Enzymatic protien (pump)
• Linker protein
• Carbohydrates comprise 3%–5% of cell membranes.
They consist of glycolipids & glycoproteins which
forms glycocalyx coat on the surface of plasma
membrane.

– carries surface receptors that are involved in molecular


recognition.
Arrangement of the proteins and lipids in a membrane
Fluid Mosaic Model (Singer and Nicolson- 1972)
All membranes have the general structure, which has come to be
known as the fluid-mosaic model in which membrane proteins float
in a sea of lipid.
• According to fluid mosaic model of Singer & Nicolson

– membranes possess fluid structures with continuous but


stable lipid bilayer, studded with an array of membrane-
associated or membrane spanning proteins.

– Membrane fluidity is determined by the degree of


unsaturation of fatty acids.
– Membranes are structurally and functionally asymmetrical.
– Membranes are also electrically polarised, with inside
being negative with respect to exterior.
Cytoplasm
• Is that portion of the cell interior not occupied by the
nucleus.
• Is an aqueous substance containing a variety of cell
organelles & other structures.
• In eukaryotic cell, the nucleus & cytoplasm together
from the protoplasm.

• The structures dispersed in the cytoplasm can be


broadly divided into 3 groups
– Organelles
– Inclusion bodies
– Cytoskeleton
ORGANELLES
• Organelles (“Little organs”)
• Each organelle is a separate compartment within the cell that is
enclosed by a membrane similar to the plasma membrane.

1. Mitochondria
2. Endoplasmic
Reticulum (ER)
3. Golgi Apparatus (GA)
4. Lysosomes
5. Peroxisome

Ribosomes, centrioles and vaults are


nonmembranous organelles.
Mitochondria (Respiratory Organelle)
• About 2 µm long & 0.5–1 µm in diameter
• Comprises of:
– A smooth outer membrane
– A highly folded inner membrane with invaginations, called
cristae. It contains five complexes of integral membrane
proteins
• NADH dehydrogenase, succinate dehydrogenase,
cytochrome c reductase, cytochrome c oxidase and ATP
synthase (oxidative phosphorylation)

– An internal gel-like matrix space


• Contains enzymes of tricarboxylic acid cycle; beta oxidation
of fatty acids; urea formation; Gluconeogenesis enzymes;
• The mitochondrial genome consists of 5–10 identical circular
double-stranded DNA molecules.
• Mitochondria replicate, transcribe and translate their DNA
independently of nuclear DNA.
• Mitochondrial DNA is inherited maternally

contain crucial proteins (Electron


transport proteins) that converts
energy in food into usable form

contains enzymes involved in kreb’s cycle & fatty acid oxidation;


also contains several DNA strands, ribosomes & enzymes
Endoplasmic reticulum
• Is a network of membrane-enclosed sacs or tubules that extend
throughout the cytoplasm and connect to the nuclear envelope
• Is primarily a protein & lipid manufacturing factory.
• Two types: Rough ER & Smooth ER
Rough ER Smooth ER

•The outer surface of membrane is studded •Does not contain ribosomes .


with ribosomes. •It is abundant in cells specialize in lipid
• Unattached or “free” ribosomes are metabolism
dispersed throughout the cytosol. •Adrenal gland cells(extensive SER)
Ovaries & testes (well developed SER)

Functions Functions
The Rough ER in association with its 1. In liver cells, SER contain enzymes for
ribosomes, synthesizes & releases a variety detoxifying harmful substances.
of new proteins into the ER lumen for two
main purposes: 2. Muscle cells have modified SER-
Sarcoplasmic Reticulum which stores
1. Some are destined for export to the cell’s calcium that plays an important role in
exterior as secretory products (hormones the process of muscle contraction.
or enzymes)
2. Other are transported to sites within the 3. Hydrophobic molecules can be converted
cell in constructing new cellular to water-soluble molecules in the SER,
membrane (either new plasma thus facilitating their excretion from the
membrane or new organelle membrane) body by the liver & kidneys.
GOLGI APPARATUS (GA)
• Golgi apparatus is an organelle involved in modification
of complex molecules.
• Three levels of organisation
– Cisternae: flattened sac-like membranes
– Dictyosomes: stacks of cisternae
– Golgi complex: an association of dictyosomes
• GA appears as a stack of four to six cisternae.
• It is concerned with posttranslational modification of
proteins, including

– O-glycosylation to form glycoproteins


– Proteoglycan formation
– Sulphation of sugars and tyrosine residues
• Membranous vesicles with new proteins bud off from the granular ER
& fuse with cistern on Cis side of GA. The proteins are then passed to
cistern on Trans side, from which vesicles branch off into cytoplasm.

Functions of GA
•Site for packaging of secretory
products into secretory granules.

•Site for incorporation of


carbohydrates into newly synthesized
proteins (glycoproteins)

•Lysosomal enzymes are formed

•Transports material to other


organelles & cell surface.
Lysosomes (Lys means “break down”, some means “body”)
• Membrane bound organelles with an acidic interior
(pH ~4.5)

• Are vesicular organelles that breaks off from the GA


& then disperse throughout the cytoplasm.

• These are filled with large number of small granules,


containing variety of enzymes (lysozymes)
• For examples
1. α galactosidase A deficiency causes Fabry disease
2. β galactocerebrosidase deficiency causes Gaucher disease
3. Tay–Sachs disease, which causes mental retardation & blindness.
It is caused by loss of hexosaminidase A {enzyme that catalyzes
biodegradation of gangliosides (fatty acid derivatives)}
by release of enzymes
through exocytosis.

5.Metabolic functions: break down


of stored glycogen, & intracellular
digestion of proteins, carbohydrates,
lipids and nucleic acids.
Peroxisome (Microbodies)
Are round membrane bound organelles, with an average diameter of 0.5 µm
Functions:
 Cholesterol synthesis;

 Bile acid synthesis

 Beta oxidation of fatty acids


 Conversion of amino acids into
glucose
 Render dangerous cellular free
radicals (O2- ,OH-) harmless by
converting them to H2O2 & then
to water & oxygen.
Numerous in Liver and Kidney

Similar to lysosomes , they are membrane enclosed sacs containing


enzymes.Unlike lysosomes they contain several powerful oxidative enzymes-
catalase, D-amino oxidase and urate oxidase.
Ribosomes
• Are the protein factories of a cell (about 20nm in
diameter)

• Composed of two parts- 60S and 40S. It contains 65%


RNA and 35% protein.

• On ribosomes, protein molecules are synthesized from


amino acids, using genetic information carried by RNA
messenger molecules from DNA in the nucleus.
Vaults (cellular trucks)
• Vaults are shaped like octagonal barrels.

• Enter nuclear pores, pick up molecules


synthesized in nucleus and deliver them
elsewhere in the cell.

• They carry messenger RNA from nucleus to the


ribosomal sites of protein synthesis within the
cytoplasm.
NUCLEUS
• Spherical or oval structure, usually located near the center of the
cell.

Surrounded by a double- layered membrane, the nuclear envelope (pierced


by many nuclear pores allowing necessary traffic to move between the
nucleus & the cytoplasm)
Houses the cell genetic material, DNA
Directs protein synthesis
Genetic blueprint during cell replication
Nucleolus

Function:
Site of ribosomal RNA synthesis. Assembles RNA and protein components
of ribosomal subunits, which then move to the cytoplasm through nuclear
pores.
CYTOSKELETON
• Is a complex network of fibres that maintains the
structure of the cell & allows it to change shape &
move.
1. Microfilaments:
(7 nm diameter) containing polarised alpha-helical double-stranded
polymers of actin.

2. Intermediate filaments:
(10 nm diameter), which are tissue-specific.

3. Microtubules:
(25 nm diameter) containing tubulin monomers.
Cytokeratin (epithelium)
desmin (muscle)
neurofilaments (nerve)

Microtubule based structures include


cilia, axons and mitotic spindles.
Microfilaments (Actin)

Contractile protein
Intermediate filaments
are primarily structural in function

They links interior of cell to


adjacent cells & surrounding
extracellular matrix via
desmosomes &
hemidesmosomes,respectively

Stained cell showing the intermediate filaments


Microtubules
• Microtubules serve multiple functions within
the cell
– intracellular transport of vesicles

– movement of cilia & flagella (e.g., tail of


spermatozoa) Dynein is the motor protein

– chromosome movement during mitosis & meiosis


Intracellular transport of vesicles
Secretory vesicles are transported from cell body along
“microtubular highway” to terminal. Vesicles containing debris are
being transported in opposite direction for degradation in cell body.

Uses feet to step on one


tubulin molecule after another

Microtubule motor proteins are dyneins and


kinesins. They translocate along microtubules in
opposite directions
(Microtubule)
Each microtubule (tubulin) pair has an inner &
outer cross-arm-dyneins with ATPase activity.
Series of radial spokes connects with central pair,
preventing buckling when the cilium bends.

ATPase activity

9+2 array

Immotile cilia syndrome (Kartagener's syndrome ) is associated


with lack of dynein cross-arms or radial spokes.
Centriole
(Microtubule)

Microtubules are target of a number of antitumor drugs


(vincristine, taxol)- impairs cell division in highly mitotic tumor
cells
Functions of Cytoskeleton
Serves as cell’s bone and muscle
Microfilaments:
– Play a vital role in various cellular contractile systems: muscle
contraction, amoeboid movement (Directional motility)
– Serves as a mechanical stiffener for microvilli

Intermediate filaments:
– Help resist mechanical stress
– Cell–cell & cell–extracellular matrix adherence

Microtubules:
– Intracellular movements (organelle, protein & vesicle transport)
– Structural backbone of cilia and flagella (beating movements on cell
surfaces)
– Spindle assembly & chromosome movement during mitosis
Microtrabecular lattice
Thank You

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