02 cell physiology

8/3/2019 02 Cell Physiology

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Cellthe basic structural and functional unit of living organism

Some Vital Processes of Living Organisms Respiration

Circulation

Digestion & Absorption

Excretion

Reproduction

Unicellular organisms: All vital processes occur in a single cell. e.g. Amoeba

Multicellular organism: Specialized systems take over specific functions.

Cells becomes specialized; organized into specific tissues, organs and

hence systems.

In humans,

Gastrointestinal system digestion and absorption

Cardiovascular systemtransport blood around the body;

perfuse the tissues

Respiratory system supply O and removes CO

Urinary system excrete waste products; conserve volume

and composition of body fluids

Reproduction perpetuate speciesControl systems

Nervous system (Quick component)

Endocrine system (Slow component)

Cells vary greatly in their size and shape. No cell can be referred to as the typical

cell. But there are many features in common to all cells for maintenance of each

cell's life

Cell Structure and FunctionChemical structure (chemical composition)

The cell is composed offive basic substances:-

1. Water (70-80%) which acts as a medium for chemical reactions and transport

of substances.

2. Electrolytes:

Cat-ions: K+, Na+, Mg++

An-ions: HCO3, PO4, Cl

3. Proteins

4. Lipids and5. Carbohydrates


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Cytoplasmic

MembranousNon-

membranouscell membrane

endoplasmic

reticulum

Golgi apparatus or

complex

mitochondria

lysosomes

peroxisomes

ribosomes

centrioles

microtubules,

microfilaments

Nuclear

Membranous

Non-membranous

nuclear membrane (or)envelope

chromati

n

nucleolus

Physical structure

1. Organelles are the living specialized structural parts ofcytoplasm and

nucleus. Organelles can be either membranous or non-membranous.

Cytoplasmic membranous organelles: cell membrane, endoplasmic

reticulum, mitochondria, Golgi

apparatus or complex, lysosomes and

peroxisomes

Cytoplasmic non-membranous organelles: ribosomes, centrioles,

microtubules and microfilaments

Nuclear membranous organelle: nuclear membrane or envelope

Nuclear non-membranous organelles: chromatin and nucleolus

2. Inclusion bodies: non-living temporary components of cytoplasm

viz. lipid globules, glycogen granules, secretory granules.

Cell membrane the membrane surrounding the cell and the membrane of other organelles

have many features in common also called the plasma membrane (or) unit membrane

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Structure

it is a dynamic, rigid, semi-permeable structure

~7.5 to 10 nm thick

composed of: proteins

lipids

phospholipids

cholesterol

Lipids

phospholipids have the shape that resembles a clothespin

they exists as a bimolecular layerwith:

the polar, hydrophilic (water soluble) heads (phosphate portion) facing:

(1) the aqueous medium that bathes the exterior of the cell, and

(2) the aqueous cytoplasm

the non-polar, hydrophobic (water-insoluble) tails (fatty acid chains)

facing each other in the middle.

This arrangement imparts the fluidityto the lipid bilayer.

Substances which are not lipid soluble have difficulty passing through the

hydrophobic interior. This contributes towards selective permeabilityof the

cell membrane.

Globular Proteins are embedded in the fluid phospholipid bilayer matrix.

Two types:1. Integral proteins:

They pass through the membrane and are the integral components of the

membrane.

Many of them have specific functions:

e.g. transport proteins: contribute towards selective permeability of the cell

membrane

2. Peripheral proteins:

They stud the inside and the outside of the membrane.

They are weakly bound the hydrophilic regions of specific integral proteins.

Peripheral proteins held by glycosylphosphatidyl inositol anchors

include:

enzymes such as alkaline phosphatase

various antigens

a number of cell adhesion molecules

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Functions of Cell Membrane

1. By forming a closed compartment around the cell, it allows cell

individuality and maintains cell integrity.

2. Transport of substances into and out of the cell

This is governed by the selective permeability of the cell membrane

2.1. Some proteins in the cell membrane function as "transport proteins" and

they act as:

(a) Channels: through which specific ions diffuse.

Some channels are "continuously open".

Some channels are "gated" i.e. they can be opened or closed by:

(i) changes in the electrical potential (voltage) across the cell membrane

(voltage-gated channels)

(ii) binding of chemicals (ligands) such as hormones or neurotransmitters

(ligand-gated or chemically-gated channels)

(iii) other stimuli such as mechanical stretch. (mechanically-gated

channels)(b) Carriers: they bind to the substances and translocate them from one

side of the membrane to the other side. Carriers moving the

substances along their concentration gradient facilitate diffusion

of these substances.

(c) Pumps: these are carriers that move the substances against their

concentration gradient. They can hydrolyse energy phosphates

(e.g. they have adenosine triphosphatase, ATPase, activity) and

use the liberated energy for uphill transport of ions across the

membrane. e.g. sodium-potassium ATPase pump

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Transport proteins (carriers or pumps) may also be classified in a functional sense

according to the number of substances moved and the direction of movement:

A "uniport" transports only one substance (direction depends on the

gradient).e.g. glucose transporter (GLUT) in muscle facilitates the

glucose diffusion by moving glucose into the cells

"Co-transporters" simultaneously transport more than one substance, and

can be sub-categorized into two types:

(1) a "symport" moves two or more different substances in the

same direction

(2) an "antiport" (countertransporter) moves two or more different

substances in the opposite directions.

e.g.i. Na-Ca antiport moves 2 Na into and one Ca out

of cardiac muscle cellsii. Band 3 protein (anion exchanger) in RBCs and acid-

secreting cells of the stomach moves one HCO and one

Cl ion in opposite directions along their concentration

gradients

iii. Na-K pump moves Na and K in opposite directions

against their concentration gradient.

2.2. The cell membrane exhibits endocytosis (pinocytosis=cell drinking,

phagocytosis=cell eating) and exocytosis (emeiocytosis=cell vomiting),

transporting particulate matter and proteins into or out of the cells.

3. Other proteins in the cell membrane function as

(a) receptors, which provide binding sites for many molecules e.g. hormones

and drugs

(b) enzymes, catalyzing reactions at the surfaces of the membrane

(c) antigens, carrying immunological identification marks e.g. blood group

antigens

(d) cell adhesion molecules (CAMs)

These molecules attach cells to each other and to the basement

membrane, forming intercellular connections which give strength and

stability to tissues. Many CAMs pass through the cell membrane and areanchored to the cytoskeleton. Others bind to large molecules in the

extracellular matrix. They play important role in:

i. development and formation of nervous system and other tissues

ii. holding tissues together for structural support (by CAMs called

cadherins)

iii. inflammation

iv. wound healing and scar formation

v. spread of tumors

vi. transmission of signals into and out of the cells

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INTERCELLULAR CONNECTIONS

Two types

1. The junctions that the cells together giving strength and stability to tissues

a. Tight junctions (zonula occludens) made up of protein ridges - half from one cell and half from adjacent cell-

strongly held together

found in apical margins of epithelial cells in the intestinal mucosa, renal

tubules and the choroid plexus

form a barrier to the movement of ions and other solutes from one side of

the epithelium to the other

but permit passage of some ions and solutes between cells (Paracellular

pathway) although the degree of leakiness varies from site to site

b. Desmosomes

spot-like patches characterized by apposed thickening of the membranes

of two adjacent cells

c. Hemi-desmosomes

half desmosomes that attach cells to an underlying basal lamina

d. Zonular adherans

continuous structures on the basal side of the zonular occludens

major site of attachment for intracellular myofilaments

2. The junctions that permit transfer of ions and molecules from one cell to another

(Gap junctions)

forms a cytoplasmic "tunnel" for diffusion of small molecules (< 1000 Da)between two neighboring cells

consists of hexagonal arrays of protein units called connexons in the

membrane of each cell, lining up with each other forming a single channel

bridging the membranes of two cells

permit substances (ions, sugars, amino-acids) to pass between cells without

entering the ECF, enabling rapid propagation of electrical activity from cell to

cell and the exchange of chemical substances

found in cardiac and smooth muscles (forms the physical basis of "functional

syncytium")

ENDOPLASMIC RETICULUM it is a complex series of tubules extending throughout the cytoplasm.

the walls of the tubules are made up of unit membrane and is continuous with

the outer nuclear membrane, golgi apparatus and cell membrane.

serves as "intracellular circulatory system"

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Two types of ER

1. Granular (or) Rough-surfaced Endoplasmic Reticulum

granules called ribosomes are attached to the cytoplasmic side of themembrane

the attached ribosomes are the site of synthesis of proteins such as

hormones that are secreted by the cell and proteins that are segregated in

lysosomes

the polypeptide chains that form these proteins are extruded into the ER

2. Agranular (or) Smooth-surfaced Endoplasmic Reticulum

lacks granules or ribosomes

Functions:

a. Metabolic function: as site of

i. steroid synthesis (in steroid secreting cells)

ii. detoxification (e.g. liver cells)

iii. glycoprotein synthesis

b. as Sarcoplasmic Reticulum, plays important role in initiating muscle

contraction and relaxation of cardiac muscle and skeletal muscle

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Golgi apparatus (Golgi complex or Golgi bodies) a collection of membrane enclosed sacs (cisterns) that are stacked like

dinner plates

continuous with the ER and is usually located near the nucleus particularly prominent in actively secreting cells

polarized (cis- = same: on the side of nucleus; trans-= opposite: on

opposite site)

Membranous vesicles containing newly synthesized proteins bud off from

the granular endoplasmic reticulum and fuse with the Golgi apparatus on

the cis- side. Then, the proteins are passed on to the cistern on the trans

side. During transit, proteins are provided the code for their final

destination (e.g. proteins for lysosomes, proteins to be secreted etc.) and

the modified proteins are repackaged into vesicles.

Function:

package the proteins with membranes and modifies their carbohydrate moieties,

preparing them for their final destination

Mitochondria(singular: mitochondrion)

Mitochondria are present in almost all cells

The more active the cell, the greater the number of mitochondria.

Structure

Sausage-shaped structure

made up of double layer of unit membrane

The outer membrane

smooth

contains enzymes of biologic oxidation

The inner membrane

folded into projections called cristae mitochondriales

The space between the membranes: intercristal space

The space surrounding the cristae: matrix

contains enzymes of Krebs citric acid cycle

On the cristae: repeating units

contains enzymes of respiratory chain & ATP synthase

These enzymes and the enzymes of Krebs Citric Acid Cycle convert the

products of carbohydrate, fat and protein metabolism (oxidation) to CO

and water. Electrons are transferred along the respiratory-enzyme chain

resulting in the synthesis of the high energy phosphate compound,

adenosine triphosphate (ATP). The process is known as oxidativephosphorylation. During the process, protons are pumped from the matrix

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into the intercristal space, and the protons diffusing back by its own

gradient drive ATP synthase for new ATP synthesis.

Functions:

1. Mitochondria are power generating units of the cell because they produce ATP

(essential for aerobic energy production)

2. Mitochondria contain DNA which represents a second genetic system in the

cell. The DNA has cyclical arrangement (normal nuclear DNA: double helical

arrangement) and inherited only from mother. DNA repair system is poorly

developed. higher mutation rate leading to diseases such as myopathies and

are associated with aging (senescence) and diabetes mellitus.

3. Mitochondria can serve as an intracellular storage site for Ca.

Lysosomes large irregular structures surrounded by unit membrane

each contains a variety of enzymes that can cause destruction of most cellular

components

ribonucleases

deoxyribonucleases

phosphatases

glycosidases

arylsulfatases

collagenases

cathepsins

the interior is more acidic than the cytoplasm (~pH 4.5)

Functions:

function as the digestive system of the cell

1. Defence and scavenger function

by digesting the phagocytosed foreign particles such as bacteria. Some

products of digestion are absorbed through the wall of the vacuole and

some are excreted by exocytosis

2. Engulfment and removal of the worn-out components of the cell

3. Autolysis of dead cells

4. help in cellular differentiation and regression of tissues e.g. involution of uterus

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Lysosomal dysfunction

In vitamin A intoxication and certain other conditions, lysosomal

membranes break down with the release of enzymes into the cytoplasm

thereby destroying cellular components. In gout, phagocytosis of uric acid crystals by neutrophils triggers the

release of lysosomal enzymes that contribute to inflammation of the joints.

Congenital absence of any one of the lysosomal enzymes leads to

engorgement of the lysosome with the material the enzyme normally

digests and eventual disruption of the cell (lysosomal storage diseases)

Peroxisomes about 0.5 m in diameter surrounded by unit membrane

contain various oxidases (which catalyze reactions generating HO )and

catalase (which converts HO to O and HO

more common in liver and kidneys

may be involved in gluconeogenesis

destroy a number of compounds and detoxify fatty acids

metabolize ethanol to acetaldehyde

Cytoplasmic non-membranous organelles

Ribosomes are granules with two subunits: 40s and 60s

the site of protein synthesis

contains RNA (65%) and protein (35%)

Ribosomes attached to the ER synthesize proteins to be secreted by the cell.

(e.g. hormones)

Free ribosomes in the cytoplasm synthesize proteins to be utilized within the

cell. (e.g. haemoglobin)

Centrioles a pair of short cylindrical structures located between the golgi complex and

nucleus arranged at right angles to each other

the wall is made up of microtubules

Function:

concerned with movement of chromosomes during cell division forming

poles of the mitotic spindle

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Microtubules and microfilamentsMicrotubules are long, hollow structures about 15 nm in diameter.Microfilaments are long, solid structures about 4-6 nm in diameter.

Functions:

Microtubules provide tracks along which secretory granules are moved from

one part of the cell to another. Protein molecules with ATPase activity that

move various substances along microtubules are called molecular motors

(kinesin and dynein)

Microtubules form mitotic spindles which move chromosomes during cell

division, mitosis. Microtubules, microfilaments and proteins that tie them together to form the

skeleton of the cell. The cytoskeleton not only maintains shape but also permit

to change shape and move.

Microfilaments are made up of actin. All cells contain actin and a variety of

actin-binding proteins, including myosin (an actin-based motor). They play a

role in:

muscle contraction

movement of microvilli in the intestinal mucosa

movement of the cell and

clot retraction Intermediate filaments connect the nuclear membrane to the cell membrane,

and also help the cell to resist external pressure. Cells rupture more easily and

skin blisters are common when these filaments are absent or abnormal.

NucleusA nucleus, the central information centre, is present in all animal cells that divide.

It consists of:

1. Nuclear membranous organelle: Nuclear membrane or envelope2. Nuclear non-membranous organelles: Chromatin and Nucleolus

1. Nuclear membrane

It is a double unit membrane, 25~40nm thick, enclosing a space called the

peri-nuclear cistern. The pores in the nuclear membrane are closed by a

thin membrane. The membrane permits passage of molecules as large as

RNA.

2. Nuclear non-membranous organelles:

a. Chromatin

Chromatin are granules of dark, densely stained particles which

condense to form chromosomes during cell division

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Chromosomes are made up of DNA and a basic protein called histone.

The chromosomes carry the genetic message, the complete blueprint

for all the inheritable characteristics of the cell.

The functional unit of DNA is a gene which contains the geneticinformation required to form one polypeptide or protein molecule (e.g.

all the enzymes which control the metabolism of the cell)

Human have 46 chromosomes, 22 pairs of somatic chromosomes

(autosomes) and 2 sex chromosomes (X and Y in males; two X in

females).

Total number

of

chromosome

s

Autosome Sex chromosome Ploidy

Somaticcell

46(23 pairs)

44(22 pairs)

2(1 pair)

(XY in male, XX in

female)

Diploid

Germ cell 23 22

(not in

pairs)

1 Haploid

ploidy = the multiple of the basic number of chromosomes in a cell

The complete genetic information is represented by the haploid number of

chromosomes (~3x10 base pairs in 23 separate molecules)

b. Nucleolus

a patch-work of granules with no limiting membrane. The granules are rich

in RNA.

Functions:

the site of synthesis of ribosomal RNA (rRNA)

temporary storage of messenger RNA (mRNA)

Deoxyribonucleic acid (DNA) a double helix formed by 2 chains of polydeoxyribonucleotides held

together by hydrogen bonds

made up of

phosphoric acid

pentose sugar

nitrogenous base

Purines Adenine & Guanine

Pyrimidines Cytocine & Thymine

Adenine always pairs with Thymine (A : T)

Guanine always pairs with Cytosine (G : C)

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The total number of purines = the total number of pyrimidines

The two chains are:

complementary (with regards to base pairing)

anti-parallel (oriented in opposite directions)

Each chain is made up of deoxyribonucleotide units linked by 3',5'-

phosphodiester bonds.

The genetic message is coded by the sequence of the bases in the

deoxyribonucleoide chains.

The message is transferred to the sites of protein synthesis by RNA. The

text of the message is the order in which the amino acids are lined up in

the protein synthesized.

Function:

carrier of genetic information

serves as template for replication (formation of new DNA during cell

division)

serves as template for formation of RNA

responsible for maintenance of the species (passed from one generation to

the next)

highly preserved through generations

Ribonucleic acid (RNA)

A single strand of ribonucleotides, made up of:

phosphoric acid

pentose (ribose) sugar

nitrogenous base

purines: Adenine, Guanine

pyrimidines: Thymine, Uracil

mainly present in the cytoplasm

1. Ribosomal RNA (rRNA)

found in ribosomes (Ribosomes contains 65% RNA and 35% proteins)

involved in the translation of genetic message

2. Transfer RNA (tRNA) (soluble or acceptor RNA)

at least 20 tRNA molecules in every cell (one for each of the 20 amino

acids)

tRNA is arranged in clover leaf structure

tRNA molecules carry activated specific amino acids to the sites of protein

synthesis (=ribosomes)

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serves as adaptors for translation of the information in mRNA into specific

sequence of amino acids

3. Messenger RNA (mRNA) mRNA carries sequence of nucleotides complementary to the sense strand

of DNA

serves as messenger conveying genetic information from the nucleus to

the ribosomes (the site of protein synthesis) where it in turn serves as

template on which a specific sequence of amino acid is polymerized to

form a specific protein.

Protein Synthesis

The Genetic Code

Genetic information lies in the sequence of nucleotides in DNA

The information is transcribed from DNA to mRNA.

Each information code word exists for each amino acid.

The code word is termed codon and consists of a triplet of nucleotides

(either A, C, G or U).

there are 64 (= 4) possible codons.

61 codes for amino acids.

3 serves as terminating signals or nonsense codons i.e. translation stops

when it encounters stop codons (UAA, UAG, UGA) More than one codon codes for a given amino acids. e.g. Both UUU and

UUC stands for phenylalanine; six codons codes for serine.

The process of protein synthesis

4 main stages:

1. Transcription

2. Post-transcriptional modification

3. Translation

4. Post-translational modification

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1. Transcription

In transcription, the code (information) on the sense strand of DNA

(template) is transcribed into a sequence of nucleotides (mRNA) by theaction of DNA-dependent RNA polymerase.

The synthesized mRNA is also called pre-mRNA or hnRNA (heterogeneous

nuclear RNA).

2. Post-transcriptional modification

The newly synthesized mRNA is processed before it is released into the

cytoplasm. The mRNA thus formed is called the definitive mRNA.

3. Translation

This step takes place in the ribosomes. The information carried by the

mRNA is translated from the linear sequence of codons (nucleotide triplets)

into a linear sequence of amino acids (peptides or proteins). tRNA, eachloaded with its specific amino acid, serves as adaptors for assembling of

amino acids.

4. Post-translational modification

The newly formed polypeptide chain is modified by one or more chemical

reactions into a final protein to achieve its functionality. e.g. prepro-insulin

pro-insulin insulin

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Transport Across Cell Membranes

1. Passive Transport Mechanisms

a. Diffusion

i. Simple or free diffusion

ii.Facilitated or carrier-mediated diffusion

iii.Non-ionic diffusion

b. Osmosis

2. Active Transport Mechanisms

a. Primary active transportb. Secondary active transport

c. Endocytosis

d. Exocytosis

Transport across epithelia

1. Filtration

2. Transcytosis (Vesicular Transport)

PASSIVE TRANSPORT MECHANISMSIn passive transport mechanisms, the movement of a substance (or) substances:

occurs spontaneously

does not depend on supply of metabolic energy and

is downhill along the gradient(s):

concentration or chemical gradient (from an area of higher concentration

to an area of lower concentration)

electrical gradient (from an area with same electrical charge to an area

with opposite charge)

pressure gradient (from an area with higher hydrostatic pressure to an

area with lower hydrostatic pressure)

osmotic gradient (from an area with lower osmotic pressure to an area with

higher osmotic pressure)

(a) Diffusion

Diffusion occurs due to random thermal motion of molecules in fluid state (liquid

or gas state).

Diffusion is the continuous random movement of molecules and ion from a region

of higher concentration to a region of lower concentration along gradients

(concentration gradient, electrical gradient, pressure gradient or osmotic

gradient).

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"flux" denotes the transfer of substances across a unit area in a given time

"influx" = flux into the cell

"efflux" = flux out of the cell

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The magnitude of diffusion across the cell membrane is governed by

(1) the properties of the substance

(i) size(ii) electrical charge

(iii) lipid solubility

(2) the barrier itself

(i) the permeability

(ii) the thickness

(iii) the cross-sectional area

(3) the forces across the cell membrane (concentration or chemical gradient,

electrical gradient)

Fick's Law of DiffusionThe net rate of diffusion (or) flux (J) across the membrane is:

directly proportionate to:

the area available for diffusion (A)

the diffusion coefficient of the membrane for the diffusing substance (D)

the concentration gradient (C)

and

inversely proportinal to:

the thickness of the membrane (or the length of diffusion path, x)

that is,

J=D A Cx

e.g.

The net rate of diffusion of oxygen in the inspired air across the pulmonary

membrane into the blood (J) will depend on:

1. the partial pressure gradient (the difference in partial pressure) between

the air and blood (P)

2. the diffusion capacity of the pulmonary membrane (lungs) to Oxygen (D)

3. the area of the pulmonary membrane (A)4. the thickness of the pulmonary membrane (x)

Any decrease in area available for diffusion (due to destruction of the lungs) or

any increase in the thickness of the pulmonary membrane due to disease process

will greatly reduce the oxygenation of blood.

Selective Permeability of Cell Membrane

Cell membranes are impermeable to proteins and other organic substances such

as phosphates. Such ions are called non-duffusible ions.

The presence of non-diffusible ions on one side of a semipermeable membrane

causes unequal distribution of of diffusible ions across the semipermeablemembrane.

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Diffusible substances

Diffusible ions can cross the cell membrane easily. These include:

Lipid soluble molecules (e.g. steroids)

Non-polar molecules (e.g. O, N) small uncharged polar molecules (e.g. CO)

Non-diffusible substances

Non-diffusible substances cannot pass through the cell membrane easily, and

thus require transport proteins to pass through.

Proteins

Small, charged substances ( e.g. ions: H, Na, K, Mg, Ca, Cl)

Large, uncharged molecules (e.g. glucose)

Polar molecules of medium to large size (e.g. organic acids s/a RCOOH)

(i) Simple diffusion

Diffusion of substances across the lipid bilayer or diffusion of ions through the ion

channels is called simple diffusion.

e.g. Steroid hormones dissolve in the lipid bilayer of the membrane and cross

with ease

e.g. K moves out of the cell membrane via K channel

(ii) Facilitated diffusion

Diffusion of large uncharged molecules across the lipid bilayer becomes greatly

facilitatedwhen they are moved across the cell membrane along their chemical

or electrical gradients by transport proteins called "carriers".

When the carrier proteins bind to the substance to be transported, their

configuration changes so that the bound substance is moved from one side of the

membrane to the other.

e.g. Transport of glucose by the glucose transporter (GLUT), which moves the

glucose down its concentration gradient from the ECF into the cytoplasm of

the cell

(iii) Nonionic diffusion

Non-ionic diffusion is the diffusion of some weak acids and bases in the

undissociated (non-ionic) form. In the ionic form, diffusion becomes difficult.

e.g. NH3 can readily diffuse across the renal tubular cell membrane but NH ion

cannot.

(b) Osmosis

DEFINITION: If 2 solutions of equal volumes but of unequal strengths are separated

by a membrane permeable to the "solvent" (e.g. "water" in most cases) but not to

the "solute", the solvent (water) will move across the membrane from the side

with lower concentration of the solute (i.e. with higher concentration of water) to

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the other side. This type of solvent movement is known as OSMOSIS. Essentially, it is

the diffusion of water along its concentration gradient.

The pressure necessary to apply on the more concentrated solution to prevent

solvent movement is defined as the "effective osmotic pressure" of thesolution.

Osmotic pressure depends on the number of particles in a solution rather than

the type or chemical nature of particles.

The concentration of osmotically active particles is expressed in osmoles.

Osmosis is important because it is the major mechanism by which water moves

across biological membranes.

Filtration

Filtration is the process by which fluid is forced through a membrane or barrier (acapillary endothelial wall) due to the difference in hydrostatic pressure on the two

sides.

The amount of fluid filtered is proportionate to

the difference in pressure (hydrostatic pressure gradient),

the surface area and

the permeability of the membrane.

Molecules smaller than the pores of the membrane pass through along with the

fluid; larger molecules are retained.

Filtration through capillary wall is termed ultrafiltration since not only

particulate matter like blood cells but also colloids like proteins are retained.

Solvent drag

When the filtering membrane is very permeable, the amount of fluid flowing in

one direction becomes very large (bulk flow), and the solvent tends to drag along

some molecules of solute along with it. This is called "solvent drag". e.g. This is

seen in glomerular filtration where the permeability of the glomerular capillaries

is very high.

ACTIVE TRANSPORT MECHANISMSActive transport requires metabolic energy and the movement is usually uphill

i.e. against concentration or electrical gradients.

(a) Primary active transport

Active transport is carried out by "protein pumps" in the cell membranes and the

energy is supplied by adenosine triphosphate (ATP) generated by the metabolism

of cells ("metabolic energy").

Examples:

1. The sodium-potassium pump (Na+-K+ ATPase)

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It has Na+-K+ activated ATPase which catalyzes the hydrolysis of ATP to ADP

and uses the liberated energy to extrude 3Na+ from the cell and take 2K+into

it (coupling ratio = 3:2) for each molecule of ATP hydrolyzed.

It produces net movement of a positive charge out of the cell for every cycle,and creates an electrical charge difference across the cell membrane.

Therefore the pump is electrogenic.

The Na+-K+ pump is found in almost all cells. Active transport of Na+ and K+ is

one of the major energy-using processes in the body accounting for a large

part of the basal metabolism.

On average: 24% of energy utilized by the cell (~70% in neurons)

Structure:

a heterodimer (one subunit + one subunit)

subunit have intracellular binding sites for Na and ATP and extracellularbinding sites for K

Mechanism:

When 3 Na bind to their binding sites on subunit accessible only from inside

the cell, one ATP molecule also binds and converted into ADP, with a

Phosphate transferred to subunit (phosphorylation). This causes change in

configuration of the protein, extruding 3 Na into the ECF. K then binds from

ECF, dephosphorylating the subunit, which returns to previous configuration,

releasing K into the ICF.

Regulation:

Intracellular [Na]: the greater the [Na]ICF, the more the Na is pumped out

(never saturate)

Second messengers: cAMP, Diacyl glycerol (DAG)

Thyroid hormones: pump activity by stimulating new formation of Na, K

ATPase

Aldosterone increases the no. of pumps

Dopamine inhibits the pump (by phosphorylating it)

Insulin increases the pump activity.

It can be inhibited by Ouabain and Digitalis in the treatment of heart failure

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2. H+-K+ ATPase: extrudes H+ from the cells in exchange for K+

3. Ca2+ ATPase: pumps Ca2+ out of cytoplasm into the endoplasmic reticulum in

skeletal and cardiac muscle cells. This leads to muscle relaxation.4. V-ATPase: pumps H+ (protons) out of cytoplasm into organelles (lysosomes,

parts of Golgi apparatus)

5. F-ATPase (ATP synthase): pumps H from mitochondrial matrix into the

intercristal space, setting up the proton gradient essential for ATP synthesis

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(b) Secondary active transport

Some carriers transport one or more molecules against their respective

electrochemical gradient (inward or outward; active / uphill) by using the energy

in the electrochemical gradient of the other molecule or molecules to drive this

transport (outward; passive / downhill). The electrochemical gradient of the latter

molecule (Na in most cases) is maintained by ATP using pumps that transport it

out of the cell.

1. Sodium-dependent glucose transport:

The cell membranes (apical or luminal) of intestinal and renal tubular cells

contain a co-transport protein (symport) that transport glucose into the

cells only if Na binds to it.

The movement of sodium is always downhill, while the net movement of

glucose is uphill, moving from lower to higher concentration.

Na gradient is maintained by the active transport of Na out of the cell by

Na, K ATPase pump.

SGLT 2 can generate an approximate 100-fold glucose gradient

SGLT1 can generate a nearly 10,000-fold glucose gradient

assuming an intracellular [glucose] of 2 mmol/L, SGLT1 could remove

virtually all glucose from either the lumen of the small intestine or the

lumen of the proximal tubule (i.e., luminal [glucose] of 0.0002mmol/L).

2. Sodium-dependent Ca2+ transport

The cardiac muscle cell membranes contains an exchange protein (antiport)

which extrude one Ca ion against the electrochemical gradient for three Na

taken into the cell. The rate of this exchange is proportional to the concentration

gradient of Na across the cell membrane which in turn depend on the activity of

the Na, K ATPase pump.

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(c) Endocytosis

Endocytosis is the process by which proteins and large molecules enter the

cell without disruption of the cell membrane. The cell membrane folds inwards and pinches off to form a tiny sphere of

membrane (called the vesicle) which encloses the ECF and the substances

that are being transported.

With endocytosis, there is loss of cell membrane enveloping the cell. There

are 2 types:-

1. Phagocytosis (cell eating): It is the process by which large particulate

matter (i.e. not in solution in the body fluids) such as bacteria, dead tissue,

or other bits of material visible under the microscope are transported into

the cell.

e.g. phagocytosis of bacteria by macrophagesMechanism:

the particle makes contact with the cell membrane

cell membrane invaginates at the area of contact

the cell extends pseudopodia around the particle (engulfment)

pseudopodia fuses to enclose the particle within a vacuole (phagocytic

vacuole or phagosome)

phagosome fuses with lysosome (phagolysosome or digestive vacuole)

enzymatic digestion occurs followed by absorption into the cytoplasm

undigestible materials are extruded out of the cell by exocytosis (cell

defecation)

1. Pinocytosis (cell drinking): It is the process by which "large molecules in

solution" (e.g. proteins) are transported into the cell.

Mechanism:

the material (in solution) makes contact with the cell membrane

invagination occurs at the area of contact

pinching off of the invagination

formation of pinocytic vacuole

which may: pass through the cell unaltered (in case of capillaries or intestinal

wall)

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or

may combine with intracellular organelles such as lysosomes to form

digestive vacuole

Two types of Endocytosis:1. Constitutive endocytosis:

It is a continuous process that is not induced.

The uptake is simply proportionate to the concentration of the substance in the

surrounding ECF

e.g. the uptake of plasma proteins by endothelial cells of capillaries

2. Non-constitutive or receptor mediated endocytosis

It is a receptor mediated selective process

for internalization of macromolecules such as protein hormones (insulin, growth

factors), LDL, toxinsoccurs at cell membrane indentations where the protein , clathrin, accumulates

triggered by various ligands binding to their receptors on the cell surface

(d) Exocytosis (Reverse endocytosis or cell vomiting)

Exocytosis is the extrusion process by which cellular secretions (proteins and

large molecules) are liberated to the exterior. e.g. secretion of protein hormones

and enzymes.

Proteins that are secreted by cells move from the endoplasmic reticulum to the

Golgi apparatus where they are packed into secretory granules or vesicles. The

granules and vesicles move to the cell membrane. Their membrane then fuses

with the cell membrane and the area of fusion breaks down. This leaves the

contents of the granules or vesicles outside the cell and the cell membrane

intact. Exocytosis adds to the total amount of membrane enveloping the cell.

The process requires Ca2+ and energy, and "docking proteins" that dock the

secretory granules or vesicles to the cell membrane.

* Docking proteins: v-SNARE protein, t-SNARE protein

Proteins may be exocytosed:

1. with little or no prior processing or storage (Constitutive pathway)2. after processing in the secretory granules (Non-constitutive pathway)

e.g. conversion of prohormones to mature hormones

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Vesicular transport (Transcytosis or Cytopempsis)

Small amounts of protein are transported out of capillaries across endothelial

cells by endocytosis followed by exocytosis on the interstitial side of the cells. The

transport system makes use of coated vesicles and is called vesicular transport

(transcytosis or cytopempsis).

INTERCELLULAR COMMUNICATIONCells communicate with each other via "chemical messengers". Within a given

tissue, some messengers move from cell to cell via "gap junctions" without

entering the ECF.

Cells are also affected by chemical messengers secreted into the ECF. Thesechemical messengers bind to protein receptors on the surface of the cell (or) in

the cytoplasm or the nucleus of the cell, triggering a sequence of intracellular

changes that produce their physiologic effects.

There are 3 general types of intercellular communication mediated by

messengers in the ECF:

(1) Neural Communication, in which neurotransmitters are released at

synaptic junctions from nerve cells and act across a narrow synaptic cleft

on a post-synaptic cell.

(2) Endocrine Communication, in which hormones reach cells via the

circulating blood:(3) Paracrine and Autocrine communication, in which the products of cells

diffuse in the ECF to affect neighboring cells that may be some distance

away (paracrine communication) or bind to receptors on the cell that

secreted them (autocrine communication).

Some growth factors are attached extracellularly to the

transmembrane proteins of some cells. Such a factor

anchored to a cell can bind to its receptor on another cell,

linking the two. This is calledjuxtacrine communication

and may be important in growth in tissues.

Table 1 Intercellular communications

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02 cell physiology

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