CELL BIOLOGY

LEVELS OF ORGARNISATION

The human body is developed through different levels of structural organization,

anatomical structures are ‘designed’ to perform specific functions.
The human body can be studied based on six structural levels, the facts obtained help
us to understand the mechanism of disease and the structural abnormalities associated
with pathology.

The different structural development includes the following:

● Chemical
● Cell
● Tissue
● Organ
● Organ system
● Organism

❖ CHEMICAL
This is the basis of life. Structural and functional characteristics of all organisms are
determined by their chemical makeup.
The unique and complex relationship between atoms, molecules and macromolecules
in living material form a semi-fluid type of material, the cytoplasm which is the
essential material for life.

❖ CELLULAR LEVEL
Cells are the smallest most numerous, structural and functional unit of a living
system. Cells exhibit the basic characteristics of living matter. Although cells have
certain features in common, they differentiate in order to perform unique specialized
functions and they can give rise to: fat cells, bone cells, blood cell, nerve cells, muscle
cells, secretory cells etc.

❖ TISSUE LEVEL
A tissue is an organization of many similar cells that are specialized to perform a
certain function. Varying amounts and kinds of non-living intercellular substances or
matrix surrounds tissue cells.

There are four principal tissue types namely:

● Epithelial tissue
● Nervous tissue
● Muscle tissue
● Connective tissue

Together the body tissues are able to meet all the structural and functional needs of
the body. Tissues do not exist in isolation; they are instead joined to form organs that
represent discrete but functionally complex operational units.

Tissues give rise to organs. An organ is a structure formed by two or more tissues that
perform a particular function. And these include;
Brain
Heart
Kidney
Lungs

❖ ORGAN SYSTEM
An organ system is an organization of several different kinds of organs, so arranged
that together can perform a specialized function. Each organ has a special
shape, size, appearance and placement in the body that makes it efficient at
performing a unique and specialized activity. Take an example of the lung that has
got:
● Muscles and connective tissues that form many tubes to convey air
● Epithelial tissue that lines the microscopic air sacs for gaseous exchange
● Nervous tissue that permits control of air and muscular contraction

❖ SYSTEM
The system level of organization involves varying numbers and kinds of organs so
arranged that together they could perform complex functions. The functions are
designed to meet specialized needs of the living matter. There are eleven major
systems in the human body namely:

● Integumentary system (skin and its appendages)

● Skeletal system
● Muscular system
● Nervous system
● Endocrine system
● Circulatory system
● Lymphatic/immune system
● Respiratory system
● Digestive system
● Urinary system
● Reproductive system

❖ ORGANISM LEVEL
An organism is an integrated assemblage of interactive structures that are able to
survive and flourish in a hostile environment. Structure determines function and
influences the actual anatomy of an organism.

HOMEOSTASIS
This means the maintenance of a constant internal environment. The internal
environment of the body is the extra cellular fluid, in which the cells live. The ECF is
the fluid outside the cell and it constantly moves throughout the body. It includes
blood which circulates in the vascular system and the fluid between cells called
interstitial fluid.
The ECF contains nutrients, ions and all other substances necessary for the survival of
the cells. The normal healthy living of large organisms depends on the constant
maintenance of internal environment within the limits of physiological range.
If the internal environment deviates beyond the set limits, the body suffers from
malfunction or nonfunctional.
Essentially all organs and tissues of the body perform functions that help maintain the
constant conditions.
The respiratory system works in such a way that each time the blood passes through
the body, it also flows through the lungs. The blood picks up oxygen in the alveoli,
thus acquiring the oxygen needed by the cells.
As blood picks up oxygen in the lungs, carbon dioxide is released from the blood into
the lung alveoli; the respiratory movement of air into and out of the lungs carries the
carbon dioxide to the atmosphere. Carbon dioxide is the most abundant of all the end
products of metabolism.
The gastrointestinal tract provides nutrients, here different dissolved nutrients,
including carbohydrates, fatty acids, and amino acids, are absorbed from the ingested
food into the extracellular fluid of the blood.
The liver changes the chemical compositions of many of these substances to more
usable forms, and other tissues of the body—fat cells, gastrointestinal mucosa,
kidneys, and endocrine glands—help modify the absorbed substances or store them
until they are needed.
The musculoskeletal system is also important in homeostasis, were it not for the
muscles, the body could not move to the appropriate place at the appropriate time to
obtain the foods required for nutrition. The musculoskeletal system also provides
motility for protection against adverse surroundings, without which the entire body,
along with its homeostatic mechanisms, could be destroyed instantaneously.
For the case of the excretory system, passage of the blood through the kidneys
removes from the plasma most of the other substances besides carbon dioxide that are
not needed by the cells. These substances include different end products of cellular
metabolism, such as urea and uric acid; they also include excesses of ions and water
from the food that might have accumulated in the extracellular fluid. The kidneys
perform their function by first filtering large quantities of plasma through the
glomeruli into the tubules and then reabsorbing into the blood those substances
needed by the body, such as glucose, amino acids, appropriate amounts of water, and
many of the ions.
The nervous system. The nervous system is composed of three major parts: the
sensory input portion, the central nervous system (or integrative portion), and the
motor output portion. Sensory receptors detect the state of the body or the state of the
surroundings. The central nervous system is composed of the brain and spinal cord.
The brain can store information, generate thoughts, create ambition, and determine
reactions that the body performs in response to the sensations. Appropriate signals are
then transmitted through the motor output portion of the nervous system to carry out
one’s desires.

The hormonal control system. Hormones are transported in the extracellular fluid to
all parts of the body to help regulate cellular function. For instance, thyroid hormone
increases the rates of most chemical reactions in all cells, thus helping to set the
tempo of bodily activity. Insulin controls glucose metabolism; adrenocortical
hormones control sodium ion, potassium ion, and protein metabolism; and parathyroid
hormone controls bone calcium and phosphate. Thus, the hormones are a system of
regulation that complements the nervous system.
Reproduction
Sometimes reproduction is not considered a homeostatic function. It does, however,
help maintain homeostasis by generating new beings to take the place of those that are
dying. This may sound like a permissive usage of the term homeostasis, but it
illustrates that, in the final analysis, essentially all body structures are organized such
that they help maintain the automaticity and continuity of life.
Control Systems of the Body
The human body has thousands of control systems in it. The most intricate of these
are the genetic control systems that operate in all cells to help control intracellular
function as well as extracellular function.

Therefore, the ultimate goal of an organism is to have a normal healthy living, which
is achieved by the maintenance of an internal environment within the set limits.
The concept of homeostasis forms the basis of physiology because it explains why
various physiological functions are to be maintained within a normal range and in
case a function deviates from this range, how it is brought back to normal.
Understanding the concept of homeostasis also forms the basis for clinical diagnostic
procedures. For example, increased body temperature as in the case of fever, indicates
that something is wrong in the heat production-heat loss mechanism of the body. This
induces the physician to go through the diagnostic proceedings and decide about the
treatment.

The body is equipped with appropriate detectors or sensors, which can recognize the
deviation of any physiological activity from the normal limits. When detectors sense
the deviation, they alert the integrating center. The integrating center sends
information to the concerned effectors to either accelerate or inhibit the activity so
that the normalcy is restored.

COMPONENTS OF A HOMEOSTATIC SYSTEM

The homeostatic system in the body acts through self-regulating devices, which
operate in a cyclic manner. This cycle includes three components

1. Detectors or sensors, which recognize the deviation

2. Transmission of this message to an integrating unit or control center.
3. Transmission of information from control center to the effectors for correcting
the deviation.

MECHANISM OF ACTION OF HOMEOSTATIC SYSTEM

The effectors bring back the normalcy either by inhibiting and reversing the change or
by accelerating and supporting the change depending upon the requirement of the
situation.
This is achieved through a feedback mechanism. Thus, the feedback mechanism is of
two types namely
1. Negative feedback
2. Positive feedback
Negative Feedback mechanism.
This is the action of the homeostatic mechanism which occurs by inhibiting the
deviation and reversing it back to normal.
Positive Feedback mechanism
This is the action of homeostatic mechanism, which occurs by supporting and
accelerating the deviation.
The functions of positive feedback mechanism are less than those controlled by
negative feedback mechanism. One of the positive feedback mechanisms occurs
during the process of coagulation of blood.
Blood coagulation is important for the arrest of bleeding during injury. There are three
important stages of blood coagulation namely
1. Formation of prothrombin activator
2. Conversion of prothrombin to thrombin.
3. Conversion of fibrinogen to fibrin by thrombin.

In addition to converting fibrinogen into fibrin, thrombin increases the formation of

prothrombin activator. This causes formation of more and more amount of
prothrombin activator so that the process of coagulation is accelerated and blood loss
is prevented quickly.

Advantages of homeostasis
Homeostasis has survival value because it means an animal can adapt to a changing
environment. The body will attempt to maintain a norm, the desired level of a factor
to achieve homeostasis. However, it can only work within tolerable limits, where
extreme conditions can disable the negative feedback mechanism. In these instances,
death can result unless medical treatment is executed to bring the natural occurrence
of these feedback mechanisms.
 THE CELL AND ITS FUNCTION

A typical cell has a nucleus, surrounded by a nucleus membrane.

Cytoplasm is the living material surrounding the nucleus. The cytoplasm is separated
from the surrounding by a cell membrane. The cytoplasm is made up of organic
substances like carbohydrates, proteins and lipids and inorganic substances like water
and electrolytes.
The electrolytes include K+, Mg2+, phosphate, sulfate, Hco3-, Na+, Cl- and ca2+.
Water is the fluid medium of the cell and all the solid substances are either suspended
in the water or they are dissolved, water is the most abundant component to the cell.
Within the cytoplasm there are specialized structures called organelles.

The electrolytes provide inorganic chemicals for cellular reactions.

Proteins constitute 10-25% of the cell mass. The proteins can be structural or globular
proteins and the globular proteins are mainly enzymes, which catalyse chemical
reactions. Structural proteins exist as long thin filaments. Filaments can be organized
into microtubules that provide cytoskeleton they are found in cilia and spindle fibres.

The lipids are soluble in fat or organic solvents. The most important lipids in most
cells are phospholipids and cholesterol, which constitute 2% of the total cell mass.
The phospholipids and cholesterol being insoluble in water are used to form
membranous barriers that separate the different intracellular compartments. Some
cells contain large quantities of triglycerides or neutral fat; which may act as energy
reserve.

Carbohydrates have very little structural function in the cell, but they play a major
role in nutrition of the cell. The carbohydrates take up to about 1% of the cell mass.
However, glucose is always present in the surrounding extra-cellular fluid so that it is
readily available to the cell. Glycogen represents the stored carbohydrates in cells and
it also serves as energy stores.

THE CELL MEMBRANE

This separates the extra-cellular fluid and the intracellular fluid. It is a semi permeable
membrane, so there is free exchange of certain substances between the ECF and ICF

The cell membrane is composed of three types of substances namely;

- Proteins (55%)
- Lipids (45%)
- Carbohydrates (5%)
The basic structure of a cell membrane is a lipid bi-layer, which is a thin film of lipids
only two molecules thick that is continuous over the entire cell surface. Interspersed
in this lipid film are large globular protein molecules. The lipids bi-layer is composed
of almost entirely of phospholipids and cholesterol. One part of the phospholipids and
the cholesterol molecules is soluble in water, i.e hydrophilic whereas the other part is
soluble in fats, i.e. hydrophobic.
The two phospholipids layers are arranged in such ways that the hydrophobic portions
(tails) meet in the center of the cell membrane. The hydrophilic portions (heads) are in
contact with the ECF and ICF.

Cholesterol molecules are arranged in between the phospholipids molecules and they
help to “pack” the phospholipids in the membrane. So, cholesterol is responsible for
the structural integrity of the cell membrane.

The characteristic feature of the lipid layer is that it is fluid in nature and not a solid
structure. The membrane lipid layer is a major barrier impermeable to water soluble
substances like ions, glucose, urea and others. On the other hand, fat-soluble
substances such as O2, CO2 and alcohol can penetrate this lipid bi-layer with ease.

THE MEMBRANE PROTEINS

The membrane proteins are mostly glycoprotein. Two types of proteins occur:
The integral proteins traverse the whole membrane and the peripheral proteins that are
attached only to the surface.

Many of the integral proteins provide structural channels through which water-soluble
substances can diffuse (ions especially). The protein molecules have selective
properties that cause some substances to diffuse more than others.

Other integral proteins act as carrier proteins for transporting substances against a
concentration of gradients (active transport). Carrier proteins are also useful in
facilitated diffusion.

Some proteins act as receptor sites for hormones and neurotransmitters, these are
called receptors proteins.

Some protein molecules form enzymes that control chemical reactions within the cell
membrane.

Some proteins act as antigens and induce the process of antibody formation.

THE MEMBRANE CARBOHYDRATES

Throughout the surface of the cell membrane, there are some carbohydrates, which
are attached to either proteins or the lipids forming glycoproteins and glycolipids
respectively.

All these carbohydrate molecules form a thin loose covering over the entire surface of
the cell membrane called glycocalyx.

IMPORTANT FUNCTIONS OF MEMBRANE CARBOHYDRATES

- Many of them are negatively charged, which gives most cells an overall
negative surface charge that does not permit the negatively charged substances to
move out of the cell.
- The glycocalyx from neighboring cells helps in the tight fixation of cells with
one another.
- Some of the carbohydrate molecules form the receptors for some hormones.

The cell membrane has the following functions;

1. It protects the cell contents

2. It allows certain substances to diffuse through and prevents others.
3. The metabolites and other waste products from the cell are excreted out
through the cell membrane.
4. Oxygen enters the cell and CO2 leaves the cell through the cell membrane.
5. The cell membrane is responsible for the maintenance of the shape and size of
the cell.
6. Cell adhesion, it has molecules that anchor one cell to another.
7. It contains pumps which actively pump ions across the membrane
8. It is responsible for the carrier mediated transport.
9. It contains receptor sites for chemical messengers, it controls flow of
information between the cells and the environment. The receptors have the ability to
read and generate signals, so it plays a central role in biological communication.
10. It is responsible for cell recognition.
11. It has ion channels which when activated allow passage of ions into or out of
the cell.
12. It has enzymes for catalyzing reaction at the surface.

CYTOPLASM AND ITS ORGANELLES

The cytoplasm is made up of clear fluid in which minute and large particles are
dispersed together with the organelles.

The fluid part of the cytoplasm is called the cytosol and in this both the organic and
inorganic substances are dissolved. The portion of the cytoplasm just beneath the cell
membrane usually contains microfilaments composed mainly of actin filaments which
give support to the cell membrane. The zone of cytoplasm, which is fluid, is the
endoplasm.

The organelles carry out the various functions of the cell. There is constant flow of
material; between the organelles. There are two types of organelles; those that are
bound by limiting membrane and those not bound by limiting membrane.

Organelles bound by limiting membrane include:

- Endoplasmic reticulum
- Golgi apparatus
- Lysosome
- Peroxisome
- Secretory vesicles
- Mitochondria

Endoplasmic reticulum
This consists of a network of tubular and flat vesicular structures, which are
interconnected. The lumen of the endoplasmic reticulum contains a fluid medium
called the endoplasmic matrix. The ER forms the link between the nucleus and cell
membrane by connecting the cell membrane with the nucleus membrane. There are
two types of ER namely;
- RER
- SER

Rough endoplasmic reticulum (RER)

This is the part of ER to which the granular ribosomes are attached. It is also called
the granular ER. It is concerned with the synthesis of proteins in the cell.

Smooth Endoplasmic Reticulum or Agranular ER

Many enzymes are present on the outer part of the SER, which are concerned with the
various metabolic processes of the cell. The SER is concerned with the synthesis of
the lipid substances like steroid hormones, sebum, cholesterol etc. it is also involved
in the catabolism of toxic substances like drugs and carcinogens.

Golgi apparatus

This has membranes similar to those of the agranular endoplasmic reticulum. It is

usually composed of four or more stacked layers of thin, flat enclosed vesicles lying
near the nucleus. The GA is very prominent in secretory cells.

The GA functions in association with the ER. It is involved in processing,

concentrating and chemically modifying proteins by adding carbohydrates and lipids,
and delivering molecules to different parts of the cell.

The proteins synthesized in the ER are transported to GA in form of reticular vesicles.

In the GA, the reticular vesicles are processed, sorted out and packed in the form of
secretory granules, secretory vesicles, lysosomes etc

Lysosomes

These are vesicular organelles formed by the GA that then became dispersed
throughout the cytoplasm. They provide an intracellular digestive system that allows
the cell to digest and there by remove unwanted substances and structures e.g.
damaged or foreign structures.

The lysosomes are filled with hydrolytic enzymes.

Functions of lysosomes

- Digestion of proteins, carbohydrates, lipids and nucleic acids

- Destruction of bacteria and other foreign bodies
- Removal of excessive secretory products in the cells of the glands
- Removal of unwanted cells in embryo
Peroxisomes

Peroxisomes are like lysosomes but are derived from the ER. They contain oxidative
enzymes, which are concerned with the metabolism of peroxide. The H2O2 formed
from poisons or alcohols that enter the cell. They also destroy enzymes, which are
necessary for the production of H2O2

Peroxides are also concerned with gluconeogenesis

from fats and degradation of purine and fats.

Centrosome and Centrioles

The centrosome is situated close to the nucleus. It consists of 2 structures called

centrioles, which are made up of proteins. The centrioles are cylindrical in shape and
are responsible for the movement of chromosomes during cell division.

Secretory vesicles

These contain secretory substances. The SV are formed in the endoplasmic reticulum,
and are processed and packed in the GA. When necessary, the secretory vesicles are
released into the cytoplasmic or through the outer membrane into the ducts or blood.

Mitochondrion

This is a rod or oval shaped structure with a double membrane. The outer membrane
is smooth and the inner one is folded to form cristae and this covers the inner matrix
space. The cristae provide large surface area for enzymatic actions. The mitochondria
can move freely in the cytoplasm and are capable of reproducing themselves.

They contain their own DNA and ribosomes and RNA. Their main function is to
produce energy in form of ATP for the cell. The matrix of mitochondria contains
many enzymes, which are responsible for citric acid cycle, oxidative phosphorylation
(synthesis ATP).

- Succinic Dehydiagnase
- Dihydronilotinamide adenine dinucleotide (NADH)
- Dehydrogenase, Cytochome Oxidase

Ribosomes

These are granular structures with a diameter of 15nm. They contain 65% RNA and
35% proteins. Some ribosomes are attached to RER while others are present as free
ribosomes. They are concerned with protein synthesis. Ribosomes attached to RER
synthesize proteins like those present in lysosomes, cell membranes and hormones.
The free ribosomes synthesize proteins like those in peroxisomes, mitochondria and
part of hemoglobin.

Cytoskeleton
The cytoskeleton of a cell is a complex network of structures of various sizes. It
determines the shape of the cell. It is also essential for cellular movements and the
response of the cell to external stimuli. It consists of three major components;
- Microtubules
- Intermediate filaments
- Microfilaments

Microtubules

These are tubular organelles without limiting membrane with a diameter of 20 to

30nm. They are composed of protein molecules called tubulin, which are arranged in
bundles. The microtubules are mainly concerned with providing structural strength to
the cell. They also form a transport system of the cell, where by some organelles and
protein molecules move to different parts of cell through microtubules. Cilia,
centrioles and mitotic spindles are composed of stiff microtubules.

Intermediate filaments

These form a network around the nucleus and extend to the periphery of the cell.
These help to maintain the shape of the cell.

Microfilaments

These are long non-tubular organelles made up of the contractile protein called actin
and myosin.
The microfilaments of the ectoplasm contain only actin molecules and those present
in endoplasm contain both actin and myosin molecules.
The microfilaments give structural strength to the cell and are responsible for the
shape of the cell and cellular movement.

Cilia, Flagella and Microvilli

Cilia project from the surface of cells and are capable of moving, a cell may have no
cilia, have a few, or thousands of them.
Cilia function, is to move materials along the surface of the cell. Found in the oviduct,
nasal passage
.
Flagella have a structure similar to cilia but are much longer. When present there is
usually one or two. Flagella functions, to propel the cell as in the sperm cell.

Microvilli
These are cylindrical extensions of the plasma membrane, but they do not move.
Microvilli are numerous on cells that have them, and they function to increase the
surface area of cells. Microvilli are abundant on the cell that line the intestine, kidney
and other areas where absorption is important.
 THE NUCLEUS

Nucleus is present in cells, which divide and produce enzymes. The cells with a
nucleus are called eukaryotes and those are without nucleus is known as prokaryotes.
Most cells have one nucleus, but a few types’ e.g skeletal muscle cells are
multinucleated. Nucleus is normally spherical and located in the centre of the cell.

The nucleus is surrounded by a nuclear membrane, which encloses the nucleoplasm

and nucleolus. The nuclear membrane is double layered and porous in nature, so that
the nucleoplasm communicates with the cytoplasm.
The outer layer of the nuclear membrane is continuous with the ER, and, the space
between the two layers of nuclear membrane is continuous with the lumen of the
endoplasmic reticulum.

The pores of the nuclear membrane are guarded by protein molecules. The exchange
of materials between nucleoplasm and cytoplasm occur through the pores of nuclear
membrane.

Nucleoplasm in the gel like ground substance of the nucleus. It contains large
quantities of genetic material in the form DNA; which is a non-dividing cell appears
in form of threadlike material known as chromatin. The DNA carries the information
about the individual’s characteristics.

Nucleolus

One or more nucleoli are present in each nucleus. The nucleus contains RNA and
some proteins, which are similar to those found in ribosomes.
The RNA is synthesized by five different pairs of chromosomes and stored in the
nucleolus. Later it is condensed to form the sub-units of ribosomes.
The ribosomes are formed in the cytoplasm by the fusion of these sub-units. The
ribosomes play an essential role in protein synthesis.

FUNCTIONS OF NUCLEUS

Control centre for all the activities of the cell.

The genes present in the nucleus control the cell division.
The hereditary information is stored in the genes of the nucleus and transformed from
one generation of the species to another.

DNA

The genetic information of an organism is stored in the form of DNA, which forms
the genes. DNA forms the chemical basis of hereditary characters. It also forms the
carrier for genetic information to the offspring. It contains the instructions for
synthesis of proteins in the ribosomes.

DNA is present in the nucleus and mitochondria of the cell. The DNA in the nucleus
is responsible for the formation of RNA i.e mRNA, tRNA and rRNA. RNA regulates
the synthesis of proteins by ribosomes. The proteins produced in a cell function as
enzymes regulating chemical reactions or as structural component inside or outside
cells.

The ability of DNA to direct protein synthesis allows it to control the activities and
the structure of cells and therefore, structural and functional characteristics of the
entire organism.

STRUCTURE OF DNA

DNA is a double stranded nucleic acid. It is made up of pentose sugar deoxyribose;

phosphoric acid and nitrogen base, there are four different of nitrogen bases.
Each DNA molecule consists of 2 polynucleotide chains, which are coiled around
each other to form a double helix. The two chains are made up of the deoxyribose and
phosphate, and then the two strands are connected with each other, by the organic
bases. A nucleotide is made up of deoxyribose sugar, phosphate and one of the four
nitrogenic bases.
The bases are of 2 types;

Purines - Adenine (A)

- Guanine (G)

Pyrimidines - Thymine (T)

Cytosine (C)

The strands are arranged in such a way that both are bound by specific base pairs.

A purine always pairs with a pyrimidine.

A pairs with G, and T pairs with C.

GENE

A gene is a portion of DNA molecule that contains the message or code for the
synthesis of a specific protein from amino acids. The code word | cordon for DNA is
made up of 3 nucleotides determined by the bases they contain. Each cordon | code
specifies a specific amino acid.
In eukaryotic cells, portions of genes that dictate the formation of proteins are usually
broken into several segments (exons) separated by segments that are not translated
(introns).
A pre-mRNA is formed from the DNA and then the introns and some of the exons are
eliminated in the nucleus by post transcriptional processing, so that the final RNA
which enters the cytoplasm is made up of exons. Introns are eliminated and exons are
joined by several different processes.
Near the transcription start site of the gene is a promoter in which is the site at which
RNA polymerase and its cofactors bind.

There are 20 amino acids and there is a separate code for each amino acid.
The arrangement of different triplets in a portion of DNA is called a gene. These are
just instructions for synthesis of a specific protein.

RNA

The functions coded in the genes are carried out in the cytoplasm of the cell by RNA.

STRUCTURE OF RNA

Each RNA molecule consists of a single strand of polynucleotide.

Each RNA nucleotide c o n s i s t s o f a r i b o s e
- Phosphate are of the following bases;

Purines - A
G

Pyrimidines - Uracil

Cytosine.

Uracil replaces thymine of DNA; the two have similar structures.

Types of RNA

There are 3 types RNA, each one plays a specific role in protein synthesis.

mRNA
This carries the instructions in one form of base sequence for synthesis of the protein
from the DNA to the cytoplasm.

tRNA
This is responsible for decoding the genetic message present in m RNA.

rRNA
This is present within the ribosome and forms part of the structure of ribosome. It is
responsible for the assembly of protein from amino acids in ribosomes.

Protein Synthesis
This involves four steps
1. Transcription
2. Post transcriptional modification
3. Translation
4. Post translational modification

Transcription means copying. This is the first stage of protein synthesis, which
involves formation of mRNA from DNA strand.
The formation of mRNA from DNA is facilitated by the enzymes RNA polymerase.
Once formed the mRNA enters the cytoplasm and activates the ribosomes resulting in
protein synthesis.

Transcription starts at the cap site and ends about 20 bases beyond the signal sequence
AATAAA. The RNA is capped in the nucleus by addition of 7-methylguanosine
triphosphate at the 5’ end. The cap is necessary for proper binding to the ribosome.
A poly A tail of about 100 bases is added to the un translated segment at the 3’ end.
The capping and addition of poly A tail forms pre mRNA.
The pre-mRNA is processed by elimination of introns and once post transcriptional
modification is complete the mature mRNA moves to the cytoplasm.
When a definitive mRNA reaches a ribosome in the cytoplasm, it dictates the
formation of a polypeptide chain.
Amino acids in the cytoplasm are activated by combination with an enzyme adenylate
and each activated amino acid then combines with a specific molecule of tRNA.

Translation is a process where the coded instructions are converted into a sequence of
amino acids in the polypeptide chain. It involves mRNA and tRNA.
Transcription starts in the ribosome with an AUG which codes for amino acid
methionine.
The mRNA attaches to the small sub unit of the ribosome during protein synthesis,
the polypeptide chain being formed attaches onto the big sub unit and the tRNA
attaches to both.
When the mRNA is in the cytoplasm, a group of ribosomes called polysome get
attached to it. The sequence of codons in mRNA are exposed and recognized by the
sequence of the bases in tRNA.
The complementary sequence of base is called anticodon. According to the sequence
of bases in the anticodon, different amino acids are transported from the cytoplasm to
the ribosomes by the tRNA that acts as a carrier. With the help of rRNA the protein
synthesis occurs in the ribosomes.
Translation stops at the UGA, UAA or UAG stop/nonsense codons and the poly
peptide chain is released.
Post translational modification
The polypeptide chain is modified to the final protein by one or more of a
combination of reactions that include hydroxylation, carboxylation or phosphorylation
of amino acid residue; cleavage of peptide bonds that convert large polypeptide to a
smaller form and folding and packaging of the protein into its ultimate complex
configuration.

CELL GROWTH AND REPRODUCTION

Most fundamental of all living functions is growth and reproduction and both
constitute the life cycle of a cell. The process of growth and reproduction or cell
replication of successive generation of cells exhibits a cyclic pattern. The gene and
their regulatory mechanisms determine the growth characteristics of the cells and also
when or whether the cells divide to form new cells.
THE CELL THEORY
The cell theory is given in four statements:
All living creatures are made from one or more cells. All cells are basically the similar
and are produced from previously existing cells. New cell can only arise from
previously existing ones by cell division.

❖ CELL REPLICATION

The new cells necessary for growth and tissue repair are formed by mitotic cell
division (mitosis), and the sex cells necessary for reproduction are formed by meiotic
cell division (meiosis).

The cell cycle

This refers to the sequence of events that lead to cell division. It has four distinct
phases namely:
G1, S, G2 and M
G1 is a growth phase during which there is a lot of biosynthetic activities, where
enzymes required for the S phase are synthesized.
S is the synthesis phase during which the DNA replicates and there is synthesis of
histones.
G2 is also a growth phase, which also involves biosynthetic activity e.g production of
microtubules required for movement of chromosomes during division.
M is the phase where actual nuclear division takes place.
Chromosomes
Each species has a characteristic number of chromosomes. For example, maize (corn) cells
have 20 chromosomes, mice cells have 40 chromosomes, and human cells have 46
chromosomes. To view clearly the chromosomes so that they can be counted, a cell can be
treated and photographed just prior to dividing. The chromosomes can then be cut out of
the photograph and arranged in pairs. Each pair with chromosomes of the same size and
appearance is known as homologous. The resulting display of paired chromosomes is called a
karyotype. A human karyotype consists of 46 chromosomes, made up of twenty-two
homologous pairs and two sex chromosomes.
Although both male and female humans have 23 pairs of chromosomes, the chromosomes of
one pair are of unequal length in the male. The larger chromosome in this pair is called the
X chromosome and the smaller one is called the Y chromosome. Females have two X
chromosomes in the karyotype. These Y and X chromosomes are called the sex chromosomes
because they contain genes that determine sex. All the other chromosomes are called
autosomes.
Just prior to division, every chromosome is composed of two identical parts called
chromatids. The two chromatids are genetically identical; that is, they contain the genes
that control the same traits. The chromatids are constricted at the centromere.
Mitosis
When a cell divides, it gives rise to two cells, each cell having the same number of
chromosomes as the original parent cell. This kind of cell division is called mitosis.
Protozoa and many other single-celled organisms divide by mitosis.

Growth involves cell division by mitosis. Mitosis involves a number of phases as described
below:
1. Prophase: The nuclear envelope of the cell and nucleolus disappear. The nuclear material
has condensed and the chromosomes are visible with a light microscope. Centrioles move to
the opposite sides of the nucleus and form the spindle. Around each centriole is an aster.
2. Metaphase: Chromosomes attach to the spindle fibres and arrange themselves along the
equator of the spindle so that they are at right angles to the spindle fibres. The
chromosomes are now ready to divide.
3. Anaphase: The centromere divides, sister chromatids separate and move to the opposite
poles of the spindle. Once the separation is complete, the chromatids are now called
chromosomes. The chromosomes begin to uncoil and the nucleoli reappear. A nuclear
membrane begins to form around the chromosomes.
4. Telophase: A nuclear membrane forms around chromosomes at each pole; the cytoplasm
of the cell begins to cleave and divide, cytogenesis occurs resulting into two daughter cells.
Mitosis is now complete.
5. Interphase: The cell nucleus is now well defined. The nucleoli are visible and the
chromosomes have already duplicated but they cannot be seen with the light microscope
because the chromatids are uncondensed or diffuse.
Meiosis
Meiosis is a kind of cell division used to produce gametes. It has two important functions:
(1) To form haploid cells with half the normal chromosome number
(2) To rearrange the chromosome with new combination of genes (genetic recombination)
Meiosis comprises two divisions; the second is division almost similar to mitosis but the first
division is different in many respects.
Meiosis I
Interphase: (not shown) Chromosomes have duplicated but they are not yet visible except as
a mass of chromatin.
Prophase: chromatin coils into long thin chromosomes, each composed of two chromatids;
chromosomes pair up, forming a structure called a tetrad. This process is called synapsis.
Crossing over may occur at this time in which chromosomes exchange segments (see below).
Metaphase: chromosome tetrads align on the equator. Each chromosome is condensed so
they appear short and thick. Homologous chromosomes of each tetrad are poised to move
towards the opposite poles of the cell.
Anaphase: chromosomes migrate towards the two poles of the cell. Pairs of homologous
chromosomes split up.
Telophase: chromosomes arrive at the poles of the cell. Each pole of the cell has haploid
chromosome set. Note that each chromosome still consists of two sister chromatids.
Meiosis 2
Meiosis II is essentially similar to mitosis. The major difference is that meiosis II starts with a
haploid cell.
Prophase: a spindle forms and moves the chromosomes towards the middle of the cell
Metaphase: chromosomes align on the equator.
Anaphase: the centromeres of sister chromatids separate and the sister chromatids of each
pair now individual daughter chromosomes move towards opposite poles of the cell.
Telophase: nuclei form at the opposite poles of the cell and cytokinesis occurs at the same
time. There are now four daughter cells (two in our case from one daughter cell), each with
haploid number of (single) chromosomes.
Crossing Over (chiasma formation)
During prophase of the first meiotic division, the chromatids of homologous chromosomes
come to lie along side each other in a process called synapsis, so that the locus of each gene
is exactly opposite the same locus in the chromatid of the homologous chromosome.
Sometimes the chromatids break and exchange equivalent portions, i.e. ‘cross over’ from
one chromosome to its homologue and vice versa.
This exchange of genetic material occurs between non-sister homologous chromatids.
Exchanges of genetic material can also occur between sister chromatids but are not of
genetic importance since sister chromatids are identical.

Crossing over
Crossing over is a means for exchanging genes between homologous chromosomes and it is
important in increasing the amount of genetic variation. The gametes that receive these
recombined chromosomes are termed recombinant genes.
Spermatogenesis and oogenesis
The formation of sperm by the testes is called spermatogenesis and the formation of eggs by
the female ovaries is oogenesis. Both processes involve meiotic divisions. During oogenesis,
meiosis produces one large cell and a small nonviable cell called the polar body. The polar
body disintegrates and is lost.
The second meiotic division does not take place unless fertilisation occurs. However,
complete oogenesis in females results into one single viable cell and at least two nonviable
polar bodies.
In the male, the first meiotic division results into two haploid cells, each of which then goes
on to give rise to two haploid cells during the second meiotic division. The result is that four
haploid cells are produced from one original cell.
The outcome of spermatogenesis and oogenesis is the production of sex cells that have one-
half the number of chromosomes of an ordinary cell. In humans, each female egg and each
male sperm cell has 23 chromosomes.
Differences between Mitosis and Meiosis
Mitosis Meiosis
Produces genetically identical cells Produces four non-identical daughter cells
The only variation can come through genetic
mutation
Chromosome number same as parent i.e. Chromosome number is halved i.e. haploid
diploid
No chromosome combination and therefore Chromosomes are rearranged to form
no variation except through mutation combinations that are different from
parent’s, which is source of genetic
variability
Organisms that produce asexually use Organisms that produce sexually use meiosis.
mitosis. The offspring are identical Sexual reproduction involves two parents
genetically to each other and to their using gametes and fertilisation to produce a
parent; they are clones zygote
Asexual reproduction is faster; conserves Sexual reproduction is slower and more
genetic status quo. Species are not properly complex; it introduces genetic variation due
adapted to the environment to recombination in meiosis and random
fertilisation which allows species to adapt
better to environment
❖ CELL GROWTH

A newly formed cell produces new molecules from, which it constructs additional
membrane, centrioles, additional cytoplasm, and other cell structures necessary for
growth. The cell makes all the structural proteins, and enzymes needed to make lipids,
carbohydrates and other substances by using the information contained in the genes of
the DNA molecules. Thus protein synthesis takes place before any other successive
cell division takes place.

Different types of cells have variable life cycles, which may vary form few minutes to
years, depending on its function and level of activity e.g. female sex cells or ova.

CELL DIFFERENTIATION AND FUNCTIONAL SPECIALISATION

The process by which cells develop specialized structures and functions is called
differentiation. From a single cell after fertilization, mitotic cell division increases the
number of cells in the body to thousands that specialize with diverse structure and
function.
In a differentiated cell, some portions of the DNA are active and others are inactive,
the active portions and inactive portions differ with each cell type. Thus
differentiation results from the selective activation of and inactivation of segments of
DNA. The resulting differentiation produces the many cell types that function
together to make a living matter. As cells differentiate and mature, the rate at which
they divide slows or even stops.

Apoptosis
This is programmed cell death, it is a normal process by which cell numbers within
various tissues are adjusted and controlled. During development, extra tissue is
removed, such as cells between the developing fingers and toes to fine-tune the
contours of the developing fetus. In adult apoptosis eliminates cells produced by
proliferation within some adult tissues to maintain a constant number with in the
tissue.
Damaged cells or potentially dangerous cells, virus infected cell and potential cancer
cells are also eliminated.
Genes regulate Apoptosis, and the proteins coded by these genes initiate the events
that lead to cell death.

BEHAVIOUR OF PARTICLES
(a) In solution
The particles in a solution are in a continuous random movement. A particle is likely
to move into and out of an area where it is in high concentration, since there are more
particles in the area of high concentration, the total number of particles moving to
areas of lower concentrations is greater i.e. there is a net flux of ions from area of high
concentration to area of low concentration. The time required for the equilibrium to
establish is directly proportional to the square of the diffusion distance. The
magnitude of the diffusing tendency from one region to another is directly
proportional to the cross-sectional area across which diffusion occurs and the
concentration gradient, which is the difference in the concentration of the diffusing
substance divided by the thickness of the boundary (Fick’s law of diffusion).

ΔC
Thus: J == - D. A. ___
ΔX

J: net rate of diffusion

D: diffusion coefficient
A: Area
ΔC
___: Concentration gradient
ΔX

The minus sign indicates the direction of diffusion, when considering the diffusion
from high to low, the concentration gradient is negative. Diffusion is the major force
affecting the distribution of water and solutes, though the permeability of the
boundaries across which diffusion occurs in the body varies

(b) In electric field

Application of an electric potential across a membrane establishes two specific poles,
the positive and negative pole. Because of the electric charges of the ions, the
negatively charged ions will be attracted to the positive pole and repelled by the
negative charges. A concentration gradient develops in the direction opposite to that
of the electrical potential difference. The concentration difference tends to move the
ions to the left, where as the electrical potential tends to move them to the right. When
the concentration difference is high enough, the two effects balance each other.
At 37oC, the electrical potential difference of a univalent ion can be determined from
the formular or the Nernst equation based on the ratio of the concentrations of that
specific ion on the two sides of the membrane.

C1
Thus: EMF (millivolts) = +/- 61log ____
C2
Nernst is the potential level across the membrane that exactly opposes net diffusion
of a particular ion through the membrane. The greater this ratio, the greater the
tendency for the ion to diffuse in one direction, and therefore the greater the Nernst
potential required to prevent the diffusion.

GOLDMAN-HODGKIN-KATZ EQUATION
This equation gives the calculated membrane potential on the inside of the membrane
when several different ions are present e.g. sodium, chloride and potassium ions i.e.

CNa+iPNa+ + C k+i PK+ + CCl-o Pcl-

EMF (millivolts) = - 61log ______________________________
 CNa+oPNa+ + C k+o PK+ + CCl-i Pcl-

When a membrane is permeable to several different ions, the diffusion potential

depends on three factors i.e.

● The polarity of the electric charge of each ion

● The permeability of the membrane (p) to each ion
● The concentration (c) of the respective ions on the inside (i) and outside (o) of
the membrane

Deductions from Goldman-Hodgkin-Katz equation

Sodium, potassium, chloride ions are the most importantly involved ions in the
development of the resting membrane potential and the concentration gradient of each
across the membrane helps determine the voltage of the membrane potential.

The degree of importance of each in determining the membrane potential depends on

the proportionate permeability for each particular ion.

The positive ion concentration gradient from inside the membrane to the outside
causes electronegativity inside the membrane (positive ions diffuse out and carry
positive charges out but leaving the non diffusible negative ions on the inside).

Similarly, negative ion concentration gradient from outside the membrane to the
inside causes electronegativity inside the membrane (negative ions e.g. chloride ions
diffuse inside and carry negative charges inside, but leaving the non diffusible
positive ions on the outside).

Permeability of sodium potassium channels undergo rapid changes during

transmission of the impulses where as the permeability of chloride channels does not
change greatly. Thus changes in sodium and potassium permeability are primarily
responsible for signal transmission in cells.

MEASUREMENT OF CONCENTRATION
There are three main units used in measuring concentrations of solutions namely:
● Mole
● Equivalent
● Osmole

Mole: A mole is the gram-molecular weight of a substance; it is the molecular weight

of the substance in grams. It is the standard unit for expressing the amount of a
substance in the SI units. Each mole contains approximately 6×10-23 particle, a
millimole =1/1,000 of a mole and a micromole = 1/1,000,000 of a mole.

Equivalent
One equivalent (eq) is one mole of an ionized substance divided by its valency. Most
of the important solutes in the body are in charged form, this makes the concept of
electrical equivalence important. One mole of Nacl dissociates into 1 equivalent of
Na+ions and 1eq of cl- ions. One equivalent of Na+ =23g, but 1eq of ca2+ =40g/2
=20g. One milliequivalent (meq) = 1/1000 of 1equivalent.

Osmole
One osmole is 1gram molecular weight of undissociated solute. it is used to express
the concentration in terms of number of particles in a solution.
180 grams of glucose =1 osmole of glucose, but 1gm molecular weight of Nacl = 2
osmoles because the number of osmotically active particles is now twice as great as in
the undissociated glucose. Therefore 1gram molecular weight of Nacl, 58.5gm = 2
osmoles.

Osmolarity is the osmolar concentration expressed as osmoles per liter of water, and
osmolality is osmolar concentration expressed as osmoles per kg of water. The
normal osmolality of the ECF and ICF is about 300milliosmoles/kg of water. At 37oC,
a concentration of 1 osmole/liter causes 19,300mmHg osmotic pressure in the solution
and1milliosmole /liter concentration is equivalent to 19.3mmHg osmotic pressure.

● Determine the total osmotic pressure exerted by the solutes in the body fluid.
CELL JUNCTIONS

A cell junction is the connection between the neighboring cells or the contact between
the cell and extra-cellular matrix.
There are three main types namely;
- Occluding junctions
- Communicating junction
- Anchoring junction.

Occluding Junctions

These are junctions that prevent the movement of ions and molecules from one cell to
another. Tight junctions belong to this category.
Tight junctions are also called Zonula occludens. Here the cell membranes of the
adjacent cells fuse together firmly. Tight junctions occur in the apical margins of
epithelial cells in intestinal mucosa, capillary wall, renal tubule and choroids plexus.
Tight junctions in the brain capillaries form the blood brain barrier. This prevents the
entrance of many substances from capillaries blood into the brain tissues.
Only lipid soluble substances like drugs and steroid hormones can pass through the
blood brain barrier.
They prevent the movement of the ions and molecules from one to another cell.
However, in some epithelial cells some solutes can leak but in others nothing can go
through.
Prevent lateral movement of proteins in the cell membrane and this act as a fence. The
proteins are kept in apical region of the cell membrane. This helps in the maintenance
of cell polarity.

COMMUNICATING JUNCTIONS
These are junctions that permit the movement of ions and molecules from one to
another cell. Gap junctions and chemical synapses are the communicating junctions.

GAP JUNCTIONS
The membranes of 2 adjacent cells lie very close to each other and the intercellular
space is reduced from the usual size of 25nm to 3nm. The cytoplasm of the two cells
is connected by the channels formed by the membranes of both cells. Molecules can
move from one cell to another cell through these channels without having contact
with extra-cellular fluid.

Functions of Gap Junction

The channels permit the passage of glucose, amino acids, ions and other substances
with a molecular weight of about 1000.

Help in rapid propagation of action potential from one cell to another cell.

Regulation of the diameter of channels in Gap Junctions.

The diameter of the channels can be regulated by the intercellular calcium ions. When
the concentration of intercellular calcium is increased the protein submits of
connexon, surrounding the channel comes close and the diameter is reduced.
The diameter of the channel is also regulated by PH voltage, hormones or
neurotransmitter.

CHEMICAL SYNAPSE

This is a junction between a nerve fibre and muscle fibre or between two nerve fibres
through which the signals are transmitted by release of chemical transmitters.

ANCHORING JUNCTIONS

These are junctions, which provide firm structural attachments to a cell with another
cell or with extra-cellular matrix.
They are responsible for the structural integrity of the tissues and are present in tissues
which are subjected to severe mechanical stress like heart muscle, epidermis of the
skin.
The anchoring junctions are formed by the actin filament or intermediate filaments
and these are two types;
1. Actin filament attachment site
(a) Adherens junction cell to cell
(b) Focal adhesion cell to matrix

2. Intermediate filament attachment sites

(a) Desmosomes cell to cell
(b) Hemidesmosomes cell to matrix.

FOCAL ADHESIONS

These are cell to matrix junctions, which connect the actin filaments of the cell to the
extra-cellular matrix. In many places, these junctions connect the cells with their basal
lamina. The proteins involved in this junction are called integrins.

DESMOSOME

This is a cell to cell junction connecting intermediate filaments of two adjacent cells.
The membranes of two adjacent cells are thickened and become spot like patches and
the intermediate filaments are attached with these patches. The proteins involved are
mostly Catherins. These tie neighboring cells of the tissues firmly and thus provide
strength and stability to the tissue.

HEMIDESOMOME

This is a cell to matrix junction connecting the intermediate filaments of the cell to the
extra-cellular matrix. This is a half desmosome as the membrane thickening occurs in
only one cell; most found at basal lamina and the proteins involved are called
integrins.

TRANSPORT THROUGH THE CELL MEMBRANE

All cells in the body need to be supplied with essential nutrients, water, electrolytes
etc and have to get rid of many metabolic wastes.
The cells achieve this by transport mechanisms across the cell membrane.
The structure of the cell membrane is suited for the transport of substance in and out
of the cell.
The structure of the cell membrane plays an important role in the transport of various
substances between extra-cellular and inter-cellular fluids.
The lipid soluble substances like O2, Co2, and alcohol pass through the lipid layer.
The water soluble substances e.g ions, glucose etc either pass through the channels
proteins while others are transported by carrier protein molecules.
Two types of basic mechanisms are involved in the transport of substances across cell
membranes namely; passive mechanism and active mechanism.

PASSIVE TRANSPORT

This is the transport of the substances along the concentration gradient or electrical
gradient or both electrochemical gradients.
No energy is needed it is also called diffusion. There are two types of diffusion
namely; simple diffusion and facilitated diffusion. Simple diffusion occurs either
through lipid layer or protein layer of the cell membrane. The facilitated diffusion
occurs with the help of the carrier proteins of the cell membranes.

SIMPLE DIFFUSSION THROUGH LIPID LAYER

The lipid layer is permeable only to those substances which are soluble in lipid layer
e.g O2, Co2, alcohol.
The diffusion through the lipid layer in directly proportional to the solubility of the
substances in lipids O2 is highly soluble in lipids so it diffuses very rapidly through
the lipid layer.

Simple diffusion through protein layer

The protein layer of the cell membrane is permeable to water soluble substances.
Electrolytes diffuse through the protein layer.
The cell membrane has got protein channels through which water soluble substance
diffuse.
These protein channels are selectively permeable i.e. each channel can permit only
one type of ion to pass through it. And the channels are named according to two ions
diffusing through.

Regulation of the Channels

Some of the protein channels and continuously open and most of the channels are
always closed. The former are called ungated channels. The closed channels are
opened only when required, these are called gated channels. The gated channels can
either be voltage gated channels or ligand gated channels or mechanically gated.
Voltage gated channels are those which open whenever there is a change in the
electric potential. E.g in neuromuscular junction, when action potential into the axon
terminal, ca+ open and Ca+ + diffuse into the interior of the axon from the ECF.

Ligand gated channels open in presence of some hormonal substances. The hormonal
substances are called ligand. E.g during transmission of impulses through the
neuromuscular junction, acetylcholine released, causes the Na+ channels to open in
the post synaptic membrane. Na+ then diffuses into the neuromuscular junction from
the ECF.
Mechanically gated channels are opened by some mechanical factors. E.g channels
present in the pressure receptor, the receptor cells or movement of hairs of the
receptor cause.

FACILITATED DIFFUSION

The layer water soluble molecules cannot diffuse through the protein channels. Such
molecules pass through cell membrane with the help of some carrier proteins which is
faster than simple diffusion.

Glucose amino acids are transported by facilitated diffusion. These molecules bind
with receptor point of the carrier protein; some conformational changes occur in the
proteins, which are bound with the molecules to be transported. As a result of those
changes, the molecule along with the receptor point reaches the other side of the cell
membrane.

FACTORS AFFECTING RATE OF DIFFUSION

Rate of diffusion is directly proportional to the permeability of the cell membrane

Rate of diffusion is directly proportional to the body temperature increases the rate of
diffusion.

Rate diffusion in directly proportional to the diffusion gradient of the diffusing

substances. However, facilitated diffusion has some limitation beyond certain level of
concentration gradient.

It is directly proportional to the solubility of substances especially the lipid soluble

substances.

It is inversely proportional to the size of the molecules. The smaller molecules diffuse
more rapidly than slightly larger molecules.

Rate of diffusion is inversely proportional to the size of ions. Smaller ions diffuse
faster than larger ions. However, in some instances a smaller ions like Na+ may not
pass through the membrane easily as a larger K+ because Na+ have got a tendency to
gather water molecules around them, making diffusion slower.

Rate of diffusion is inversely proportional to the charge of the ions. Ions with less
change e.g Na+ diffuse faster than those with greater charge e.g Ca+ +

ACTIVE TRANSPORT

This is the movement of substances against the chemical or electrical or

electrochemical gradient with expenditure of energy.
It occurs with the help of carrier proteins. Each carrier proteins that transport only one
substance are called uniports or uniport pumps. And these carrying more than one
substance are called symports or antiports.

Mechanism of active transport

The substance to be transported combines with the carrier protein of the cell
membrane and a substance- protein complex is formed. The complex moves towards
the inner surface of the cell membrane, and the substance is released from the carrier
proteins.
The carrier protein then moves back to the outer surface of the cell membrane to
transport another molecule.
The substances transported actively may be in ionic form and non-ionic form. Ionic
substances include Na+ Ca2+, K+, H+, Cl- and I-
Non-ionic substances include glucose, amino acids and urea.
There are two types of active transport namely;
1. Primary active transport
2. Secondary active transport

Primary active transport

This is the type of active transport in which the energy is liberated directly from the
breakdown of ATP. By this method, substances like Na+ Ca2+, K+, H+, Cl- are
transported across the cell membrane.

Primary active transport of Sodium and Potassium:

Sodium-Potassium pump
Sodium and Potassium are transported across the cell membrane by means of a
common mechanism called Sodium-Potassium pump. This transports Na+ from inside
the cell to the outside and K+ from the outside to the inside of the cell. This pump is
present in all body cells.

The Sodium-Potassium pump is responsible for the distribution of Na+ and K+ ions
across the cell membrane and the development of negative electrical potential inside
the cell.

The carrier protein of Sodium-Potassium pump has got six sites, which are as follows:
● Three receptor sites for Na+ on the inner surface
● Two receptor sites for K+ on the outer surface
● One site for the enzyme adenosine triphosphatase (ATPase), which is near the
sites for Na

Mechanism of action of Sodium-Potassium pump

Three Na+ and K+ to the carrier protein activates the enzyme ATPase. ATPase causes
the break down of ATP to ADP with the release of one high energy phosphate. The
energy liberated causes some sort of conformational change in the molecule of the
carrier molecule. As a result, the outer surface of the molecule now faces inside of the
cell. And the inner surface of the protein molecule faces the outer side of the cell.

After that there is dissociation and release of ions, so Na+ are released outside and K +
are released inside (exact mechanism is not known).

When the pump works once, there is a net loss of one positively charged ion from the
cell. The continuous activity of the pumps causes development of negative potential
inside the cell. This is called the electrogenic activity of Na-k pump.

Transport of calcium ions:

Calcium is actively transported from inside to outside the cell by a calcium pump. The
energy is obtained by the break down of ATP. Ca pumps are also present in some
organelles of the cell like Sarcoplasmic reticulum in the muscles and the mitochondria
of all the cells. The pumps move Ca into the organelles.

Secondary active transport

When Sodium is transported by a carrier protein, another substance is also transported
by the same protein simultaneously, either in the same direction or in an opposite
direction.
The secondary active transport is of two types namely;
Sodium co-transport and Sodium counter transport, the two are operated by separate
carrier protein.
The protein that transports two different molecules in the same direction is called the
symport or symport pump. The one that transports two different molecules in opposite
directions is called the antiport or antiport pump.

Sodium co-transport
Sodium and another substance, are carried by the carrier protein called symport. The
energy is obtained from the diffusion process of Na due to concentration gradient
across the cell membrane. The carrier protein for Sodium co-transport has two
receptor sites on the outer surface, one for Na and the other for another molecule.
Substances carried by Na co-transport include glucose, amino acids, chloride, iodine,
iron and Urate ions.
Sodium co-transport of glucose
One Sodium ion and one glucose molecule from the extra-cellular fluid, bind with the
respective receptor sites of the carrier protein. The carrier protein is then activated and
this causes conformational changes in the carrier protein, so that Na and glucose are
released into the cell.
The co-transport of glucose occurs during the absorption of glucose from the
intestines and re-absorption of glucose from renal tubule.
Sodium co-transport of amino acids
The carrier proteins for the transport of amino acids are different from the carrier
proteins for transport of glucose. There are five sets of carrier proteins in the
membrane. Each one carries different amino acids depending upon the molecular
weight of the amino acid.
The Sodium co-transport of amino acids also occurs during the absorption of amino
acids from the intestines and re-absorption from the renal tubules.

Sodium counter transport

Here substances are transported across the cell membrane in exchange for Na+ by the
carrier protein called antiport. Examples include; Sodium-Calcium counter transport,
which is present in all cells.
Sodium-hydrogen counter transport, where H+ are exchanged for Na+ and this occurs
in the renal tubular cells. The Na+ move from the tubular lumen into the tubular cells
and H+ move from the tubular cell into the tubular lumen. Others include;
a) Sodium-magnesium counter transport
b) Calcium-magnesium counter transport
c) Calcium-potassium counter transport
d) Chloride-bicarbonate counter transport
e) Chloride-sulfate counter transport

SPECIAL CATEGORIES OF TRANSPORT

The following are the special categories of transport that exist in the body and they
include;
 a) Endocytosis
b) Exocytosis
c) Filtration
d) Osmosis

Endocytosis
This is the process by which the substances enter the cell without passing through the
membrane. There are three types of endocytosis namely;
[Link]
[Link]
[Link] mediated endocytosis

a) Pinocytosis
This is also called cell drinking. The macromolecules like bacteria and antigens enter
the cell by pinocytosis; and the macromolecules are normally in form of droplets of
fluid.
So, the droplets bind to the outer surface of the cell membrane, and the membrane
invaginates around the droplets.
The droplets are engulfed by the membrane and are converted into vesicles and
vacuoles called endosomes.
The endosomes move into the interior of the cell and come in contact with the
lysosomes of the cell. The membrane of the lysosomes rupture are activated and
released.
The enzymes breakdown the membrane of endosomes and the contents of endosomes
are released into the cell.

Phagocytosis.
This is the process by which particles larger than macromolecules are engulfed into
the cell, it is also called cell eating.
Only a few cells in the body can carry out phagocytosis, these include neutrophils,
monocytes and the tissue macrophages.
When bacteria or foreign body enters the body, the phagocytic cell sends cytoplasmic
extensions called pseudopodic around the foreign body. The particles are engulfed
inside the cell and digested.
Receptor mediated endocytosis.
There are some pits in the surface of cell membrane. These pits contain a receptor
protein called clathrin. The pits along with the receptor protein is called receptor
coated pits.
This is induced by various ligands or other substances which bind to the receptors in
the coated pits.
The ligand or substance-receptor complexes are aggregated in the coated pits.
Later, the pit is detached from the cell membrane forming the coated vesicle.
The vesicle forms endosome which moves into the deeper part of the cell and fuses
with lysosomes.
The enzymes of the lysosomes digest the membrane of endosome and the ligand or
substances are released in to cytoplasm. The transport of various types of viruses,
different toxins, the hormone insulin and nerve growth factor into the cells is carried
by receptor mediated endocytosis.
Some of the receptor coated pits in the cell membrane are coated with another protein
called caveolin instead of clathrin.
The caveolin coated pits are concerned with the transport of vitamins in to the cell.

EXOCYTOSIS
This is the process by which substances are expelled from the cell.
It is involved in the release of secretory substances from the cell.
When required the secretory vesicles containing the secretory substances move
towards the cell membrane and fuse with it. The contents are released out of the cell.
Particular ions may be required for exocytosis to take place.e.g. Ca2+ are required
during the release of neurotransmitters.
FILTRATION
This is the movement of water and solutes from an area of high hydrostatic pressure
to an area of low hydrostatic pressure.
The hydrostatic pressure is developed by the weight of the fluid.
Filtration is essential for movement of fluid along with dissolved substances from
arterial end of capillaries into the interstitium.
It also occurs in glomerulus of kidneys.
OSMOSIS
This is the movement of solvent molecules from an area of lower solute concentration
to an area of higher solute concentration across a selectively permeable membrane.
It can occur across any membrane wherever there is a difference in solute
concentration on either side of the membrane.
Osmotic pressure develops as a result of osmosis,
(pressure created by solutes)
Osmotic pressure prevents movement of water.
The osmotic pressure exerted by the colloidal substances (proteins) of the plasma is
known as oncotic pressure and it is about 25mmHg.

CELL SIGNALLING AND COMMUNICATION

Cells communicate with each other via chemical messengers, a chemical messenger
could be any one of the following:
● Amines
● Aminoacids
● Steroids
● Polypeptides
● Lipids
● Purine nucleotides
● Pyrimidine nucleotides

Major types of intercellular communication

There are three major types of intercellular communication mediated by chemical
messengers in the ECF.

(a) Neural communication

Neural transmitters are released at the synaptic junctions from nerve cells and act
across a narrow synaptic cleft on the postsynaptic cell.

(b) Endocrine communication

Secretory cells of the endocrine system send hormone (Greek homaein, ‘to excite’)
molecules by way of blood stream to signal specific target cells through out the body.
A target cell is any cell with one or more receptors for a particular hormone,
postsynaptic cells or endocrine target organs must have appropriate signal to be
influenced by the signaling signal.

(c) Paracrine communication

Certain cells produce products that diffuse in the ECF to influence neighbouring cells
that may be some distance away. Some cells secrete chemical messengers that in
some circumstance bind to the receptors on the same cell i.e. the cell that secretes the
chemical messenger (autocrine communication).
Others
● Juxtacrine communication
Some cells express a multitude of growth factors such as transforming growth factor
alpha (TGFα) on the transmembrane protein extracellular surfaces. These provide
anchorage to the cell, and then other cells have TGFα receptors. TGFα anchored to a
cell can bind to a TGFα receptor on another cell, linking them together and this is
important in providing a focus of growth in tissues.
Chemical Messengers can move from cell to cell via gap junctions without entering
the ECF. Other chemical messengers are secreted into the ECF. The chemical
messengers bind to receptors, which may be on the cell membrane or in the cytoplasm
or nucleus.

Receptors are proteins or glycoproteins that bind chemical signals to produce

response. The binding of the chemical messenger on any of the receptor triggers a
sequence of events that translate into physiologic effects. The portion of the receptor
where a chemical signal binds is a receptor site, the shape and the chemical
characteristic of each receptor site allows only specific chemical signal to bind it, but
not others. This tendency is known as specificity.

Receptor types:
a) Intracellular receptors
These are located either in the cytoplasm or nucleus. Intercellular signals e.g.
thyroxine (T4) and triidothyronine (T3) may diffuse across the membrane and bind to
the receptor sites on the intracellular receptors, receptors for these hormones are
associated with the DNA (nuclear receptor), the receptor-hormone complex increases
the synthesis of mRNA that moves to the cytoplasm and directs the synthesis of new
proteins at the ribosomes. The new synthesized protein produces a response. Some
intracellular receptors are enzymes; a signal binding to such a receptor changes the
activity of the enzyme.

(b) Membrane bound receptors

Extend across the cell membrane with their receptor sites on the surface of the cell
membrane. They respond to the intercellular chemical signals that are large, water-
soluble molecules that cannot diffuse across the cell membrane.

A Membrane receptor is in association with another protein called the heterometric G-

protein (regulatory protein) so; the chemical messenger combines with a receptor
coupled with G-proteins. The G-proteins couple the receptors to catalytic units that
catalyze the intracellular formation of the second messenger or couple the reaction
directly to the ion channels. The G-proteins translate a signal into a biologic effect
inside the cell.

A G-protein has three sub units α, β, and γ that form a complex, which binds to the
intracellular portion of the receptor molecule.

Binding of an intercellular signal to the membrane bound receptor, the G-protein

exchanges GDP for GTP (guanyl analogue of ATP), the α- subunit separates from the
β, and γ- sub units. The separated α- subunit moves freely in the cytoplasm of the cell
performing one or multiple functions depending on the specific functions of the cell.
G-proteins relay signals from over 1000 receptors and their effectors in the cell
include, ion channels and enzymes.

Depending upon the coupling of the chemical receptor on to an inhibitory (Giα) or

stimulatory (Gsα) G-protein, a 1st messenger can either increase or de crease the
concentration of the 2nd messenger, and depending upon the receptor molecule and the
specific function of the G-protein present in the cell, different types of intracellular
second messenger chemical signals are produced.

Examples of intracellular second messengers include:

● Cyclic adenosine monophosphate (cAMP)
● Cyclic guanosine monophosphate (cGMP)
● Inositoltriphospate (IP3)
● Diacylglycerol (DAG)
● Ca/calmodulin

THE CONCEPT OF SECOND MESSENGER

(Fixed membrane receptor hypothesis)
Many extracellular chemical mediators bind to the surface of transmembrane
receptors of the cell membrane, they are referred to as 1st messengers. The first
messenger delivers its chemical message to the fixed receptor in the target cell’s
membrane and triggers release of an intracellular messenger called second messenger,
thus the message is passed to into the cell where the 2nd messenger triggers the
appropriate cellular changes.

Cyclic adenosine monophosphate (cAMP)

This acts as a 2nd messenger for mainly protein –pituitary gland, parathormone,
glucagon, and catacholamines (as1st messengers). Cyclic adenosine monophosphate
(cAMP) is formed when the 1st messenger (hormone) forms a complex with the
receptor; the receptor-hormone complex activates a protein adenyl cyclase, an enzyme
in the cell membrane. Most of this enzyme protrudes into the cytoplasm of the cell
from the inner surface of the cell membrane. The activated adenyl cyclase converts
the ATP of the cytoplasm into cyclic adenosine monophosphate

Actions of cAMP
It executes the activities of the 1st messenger inside the cell by stimulating some
enzymes like protein kinase A, which phosphorylates specific proteins in the cell
leading to biochemical reactions that bring about response to the hormone. The cAMP
produces the response depending upon the functions of the target cell through
enzymes.

Some of the responses brought about by the cAMP include the following:
● Contraction and relaxation of the muscle fibers
● Alteration in the cell membrane permeability
● Synthesis of substances in the cell
● Secretion or release of substances by the target cell (exocytosis)
● Affects the epithelial tissues of the renal tubules by increasing their
permeability to water.
● And other physiologic activities of the target cell

Calcium/calmodulin system
Many ligand or potential gated ion channels act by increasing the concentration
calcium ions in the cytosol which act as a 2nd messenger along with another protein
called calmodulin or troponin. Calmodulin has 4 sites for calcium ions and any
occupation of these sites with calcium leads to activation, conformational changes
occur that initiate activation or inhibition of phosphorylation of the proteins involved
in the cell’s response.

Calmodulin complex is capable of activating the following calmodulin dependent

enzymes:

● Myosin light chain kinase, which phosphorylates myosin of the smooth

muscle that brings about contraction in smooth muscles
● Calcium/calmodulin kinase III that is involved in the process of protein
synthesis
● Calcineurin, a phosphatase that inactivates calcium ion channels by
dephosphorylylating them.
● It also plays a role in activating T-cells

The normal calcium ion concentration in most cells of the body is 10-8 to 10-7 mol/L,
not enough to activate the calmodulin system, and arise between 10-6 to 10-5 mol/L is
enough for binding to calmodulin to occur and cause all the intracellular calmodulin
actions.

Inositol triphosphate (IP3) and Diacylglycerol (DAG)

They are both formed from phosphatidylinositol diphosphate (PIP2), a phospholipid
in the cell membrane. A phosphatase C enzyme is attached to the inside of the
transmembrane receptor protein, the first messenger through the G-protein activates
the enzyme that catalyses the break down of PIP2 into Inositol triphosphate (IP3) and
Diacylglycerol (DAG).

➢ Inositol triphosphate (IP3), acts on protein kinase C and causes the

physiological response by the release of calcium ions from the mitochondria and the
sarcoplasmic reticulum. The calcium ions, then their second messenger effects like
smooth muscle contraction, and change in the cell secretion.

➢ Diacylglycerol (DAG), activates the enzyme protein kinase C, which then

phosphorylates a large number of proteins, leading to the cell’s response. The lipid
part of DAG, the arachidonic acid is a precursor for the prostaglandins and other local
hormones that cause multiple effects throughout the body.

Cyclic guanosine monophosphate (cGMP)

Some 1st chemical messengers binding with the receptor, activates G-protein that
subsequently activates the enzyme adenyl cyclase in the cell membrane. A portion of
this enzyme protrudes to the interior of the cell and causes the formation of cyclic
guanosine monophosphate (cGMP).

Like other 2nd messengers, it executes the effects of the1st chemical messengers and is
involved in the following physiologic responses:

● Light vision
Cyclic guanosine monophosphate (cGMP) in the dark acts directly on the sodium ion
channels and maintains them open. Light acts on rhodopsin in rods altering its
structure that activates the G-protein (Gt1) or transducin, which relays signals to
phosphodiesterase enzyme. The enzyme accelerates the conversion of cGMP into 5'
GMP, the decline of cGMP in the cytoplasm causes some sodium ion channels to
close and this produces hyperpolarisation potential. Thus the diminishment of sodium
ions is what excites the rods. A similar process occurs in the cone, but the mediating
protein is Gt2.

● Cyclic guanosine monophosphate (cGMP) mediates the intracellular effects of

Nitric oxide (NO) and NO-containing compounds. NO is an endothelium-derived
relaxing factor (EDRF), an intercellular messenger that regulates the diameter of
blood vessels. It is also involved in penile erection and synaptic transmission in the
brain.

● cGMP also changes the degree of or activates phosphorylation of the calcium

pumps that pump calcium into the sarcoplasmic reticulum and those that pump
calcium out of the cell itself. These effects reduce the calcium ion concentration in the
sarcoplasm, there by inhibiting contraction.