Cell
Cell
Cell
                                                                                                        1
                                 INTRODUCTION
                                 STRUCTURE OF THE CELL
                                 CELL MEMBRANE
                                 CYTOPLASM
                                 ORGANELLES IN CYTOPLASM
                                 ORGANELLES WITH LIMITING MEMBRANE
                                 ORGANELLES WITHOUT LIMITING MEMBRANE
                                 NUCLEUS
                                 DEOXYRIBONUCLEIC ACID
                                 GENE
                                 RIBONUCLEIC ACID
                                 GENE EXPRESSION
                                 GROWTH FACTORS
                                 CELL DEATH
                                 CELL ADAPTATION
                                 CELL DEGENERATION
                                 CELL AGING
                                 STEM CELLS
             FIGURE 1.1: Structure of the cell                         FIGURE 1.2: Diagram of the cell membrane
                                                                                                 Chapter 1 t Cell       5
2. Unit membrane model                                          oily structures and cholesterol helps to ‘pack’ the
                                                                phospholipids in the membrane. So, cholesterol is
In 1957, JD Robertson replaced ‘DanielliDavson model’
                                                                responsible for the structural integrity of lipid layer of the
by ‘Unit membrane model’ on the basis of electron
                                                                cell membrane.
microscopic studies.
3. Fluid mosaic model                                           Functions of Lipid Layer in Cell Membrane
Later in 1972, SJ Singer and GL Nicholson proposed ‘The         Lipid layer of the cell membrane is a semipermeable
fluid mosaic model’. According to them, the membrane            membrane and allows only the fat-soluble substances
is a fluid with mosaic of proteins (mosaic means pattern        to pass through it. Thus, the fat-soluble substances like
formed by arrangement of different colored pieces of            oxygen, carbon dioxide and alcohol can pass through
stone, tile, glass or other such materials). This model         this lipid layer. The water-soluble substances such as
is accepted by the scientists till now. In this model, the      glucose, urea and electrolytes cannot pass through this
proteins are found to float in the lipid layer instead of       layer.
forming the layers of the sandwich-type model.
                                                                Protein Layers of the Cell Membrane
Lipid Layers of the Cell Membrane
                                                                Protein layers of the cell membrane are electron-dense
The central lipid layer is a bilayered structure. This is       layers. These layers cover the two surfaces of the
formed by a thin film of lipids. The characteristic feature     central lipid layer. Protein layers give protection to the
of lipid layer is that, it is fluid in nature and not a solid   central lipid layer. The protein substances present in
structure. So, the portions of the membrane move from           these layers are mostly glycoproteins.
one point to another point along the surface of the cell.          Protein molecules are classified into two categories:
The materials dissolved in lipid layer also move to all          1. Integral proteins or transmembrane proteins.
areas of the cell membrane.                                      2. Peripheral proteins or peripheral membrane
    Major lipids are:                                               proteins.
 1. Phospholipids
 2. Cholesterol.                                                1. Integral proteins
1. Phospholipids                                                Integral or transmembrane proteins are the proteins that
                                                                pass through entire thickness of cell membrane from one
Phospholipids are the lipid substances containing phos-         side to the other side. These proteins are tightly bound
phorus and fatty acids. Aminophospholipids, sphingo-            with the cell membrane.
myelins, phosphatidylcholine, phosphatidyletholamine,               Examples of integral protein:
phosphatidylglycerol, phosphatidylserine and phos-                     i. Cell adhesion proteins
phatidylinositol are the phospholipids present in lipid
                                                                      ii. Cell junction proteins
layer of cell membrane.
                                                                     iii. Some carrier (transport) proteins
    Phospholipid molecules are arranged in two layers
(Fig. 1.3). Each phospholipid molecule resembles the                 iv. Channel proteins
headed pin in shape. The outer part of the phospholipid               v. Some hormone receptors
molecule is called the head portion and the inner portion           vi. Antigens
is called the tail portion.                                         vii. Some enzymes.
    Head portion is the polar end and it is soluble in
water and has strong affinity for water (hydrophilic). Tail
portion is the non-polar end. It is insoluble in water and
repelled by water (hydrophobic).
    Two layers of phospholipids are arranged in such a
way that the hydrophobic tail portions meet in the center
of the membrane. Hydrophilic head portions of outer
layer face the ECF and those of the inner layer face ICF
(cytoplasm).
2. Cholesterol
Cholesterol molecules are arranged in between the
phospholipid molecules. Phospholipids are soft and                        FIGURE 1.3: Lipids of the cell membrane
   6    Section 1 t General Physiology
             BOX 1.1: Cytoplasmic organelles                     between nucleus and cell membrane by connecting the
                                                                 cell membrane with the nuclear membrane.
              Organelles with limiting membrane
 1.   Endoplasmic reticulum                                      Types of Endoplasmic Reticulum
 2.   Golgi apparatus
 3.   Lysosome                                                   Endoplasmic reticulum is of two types, namely rough
 4.   Peroxisome                                                 endoplasmic reticulum and smooth endoplasmic reti-
 5.   Centrosome and centrioles                                  culum. Both the types are interconnected and continuous
 6.   Secretory vesicles                                         with one another. Depending upon the activities of the
 7.   Mitochondria
                                                                 cells, the rough endoplasmic reticulum changes to
 8.   Nucleus
                                                                 smooth endoplasmic reticulum and vice versa.
            Organelles without limiting membrane
 1. Ribosomes                                                    Rough Endoplasmic Reticulum
 2. Cytoskeleton
                                                                 It is the endoplasmic reticulum with rough, bumpy or
of endoplasmic reticulum contains a fluid medium called          bead-like appearance. Rough appearance is due to the
endoplasmic matrix. The diameter of the lumen is about           attachment of granular ribosomes to its outer surface.
400 to 700Å. The endoplasmic reticulum forms the link            Hence, it is also called the granular endoplasmic
                Organelles                                                    Functions
 Rough endoplasmic reticulum              1. Synthesis of proteins
                                          2. Degradation of wornout organelles
 Smooth endoplasmic reticulum             1. Synthesis of lipids and steroids
                                          2. Role in cellular metabolism
                                          3. Storage and metabolism of calcium
                                          4. Catabolism and detoxification of toxic substances
 Golgi apparatus                          1. Processing, packaging, labeling and delivery of proteins and lipids
 Lysosomes                                1. Degradation of macromolecules
                                          2. Degradation of wornout organelles
                                          3. Removal of excess of secretory products
                                          4. Secretion of perforin, granzymes, melanin and serotonin
 Peroxisomes                              1. Breakdown of excess fatty acids
                                          2. Detoxification of hydrogen peroxide and other metabolic products
                                          3. Oxygen utilization
                                          4. Acceleration of gluconeogenesis
                                          5. Degradation of purine to uric acid
                                          6. Role in the formation of myelin
                                          7. Role in the formation of bile acids
 Centrosome                               1. Movement of chromosomes during cell division
 Mitochondria                             1. Production of energy
                                          2. Synthesis of ATP
                                          3. Initiation of apoptosis
 Ribosomes                                1. Synthesis of proteins
 Cytoskeleton                             1. Determination of shape of the cell
                                          2. Stability of cell shape
                                          3. Cellular movements
 Nucleus                                  1. Control of all activities of the cell
                                          2. Synthesis of RNA
                                          3. Sending genetic instruction to cytoplasm for protein synthesis
                                          4. Formation of subunits of ribosomes
                                          5. Control of cell division
                                          6. Storage of hereditary information in genes (DNA)
   8    Section 1 t General Physiology
                                                               Types of Lysosomes
                                                               Lysosomes are of two types:
                                                                1. Primary lysosome, which is pinched off from Golgi
                                                                   apparatus. It is inactive in spite of having hydrolytic
                                                                   enzymes
                                                                2. Secondary lysosome, which is the active lysosome.
                                                                   It is formed by the fusion of a primary lysosome with
                                                                   phagosome or endosome (see below).
                                                               Functions of Lysosomes
                                                               Lysosomes are often called ‘garbage system’ of the cell
                                                               because of their degradation activity. About 50 different
                                                               hydrolytic enzymes, known as acid hydroxylases are
                                                               present in the lysosomes, through which lysosomes
                                                               execute their functions.
               FIGURE 1.5: Golgi apparatus                     Important lysosomal enzymes
                                                                1. Proteases, which hydrolyze the proteins into amino
1. Processing of materials                                         acids
Vesicles containing glycoproteins and lipids are                2. Lipases, which hydrolyze the lipids into fatty acids
transported into Golgi apparatus. Here, the glycoproteins          and glycerides
and lipids are modified and processed.                          3. Amylases, which hydrolyze the polysaccharides
                                                                   into glucose
2. Packaging of materials
                                                                4. Nucleases, which hydrolyze the nucleic acids into
All the processed materials are packed in the form of              mononucleotides.
secretory granules, secretory vesicles and lysosomes,
which are transported either out of the cell or to another     Mechanism of lysosomal function
part of the cell. Because of this, Golgi apparatus is called   Lysosomal functions involve two mechanisms:
the ‘post office of the cell’.                                  1. Heterophagy: Digestion of extracellular materials
3. Labeling and delivery of materials                              engulfed by the cell via endocytosis
                                                                2. Autophagy: Digestion of intracellular materials such
Finally, the Golgi apparatus sorts out the processed and
                                                                   as worn-out cytoplasmic organelles.
packed materials and labels them (such as phosphate
group), depending upon the chemical content for delivery       Specific functions of lysosomes
(distribution) to their proper destinations. Hence, the
Golgi apparatus is called ‘shipping department of the          1. Degradation of macromolecules
cell’.                                                         Macromolecules are engulfed by the cell by means of
                                                               endocytosis (phagocytosis, pinocytosis or receptor-
 LYSOSOMES                                                    mediated endocytosis: Chapter 3). The macromolecules
Lysosomes are the membrane-bound vesicular                     such as bacteria, engulfed by the cell via phagocytosis
organelles found throughout the cytoplasm. The lyso-           are called phagosomes or vacuoles. The other
somes are formed by Golgi apparatus. The enzymes               macromolecules taken inside via pinocytosis or
synthesized in rough endoplasmic reticulum are                 receptor-mediated endocytosis are called endosomes.
processed and packed in the form of small vesicles in          The primary lysosome fuses with the phagosome or
the Golgi apparatus. Then, these vesicles are pinched          endosome to form the secondary lysosome. The pH in the
off from Golgi apparatus and become the lysosomes.             secondary lysosome becomes acidic and the lysosomal
    Among the organelles of the cytoplasm, the                 enzymes are activated. The bacteria and the other
lysosomes have the thickest covering membrane. The             macromolecules are digested and degraded by these
membrane is formed by a bilayered lipid material. It has       enzymes. The secondary lysosome containing these
many small granules which contain hydrolytic enzymes.          degraded waste products moves through cytoplasm and
   10   Section 1 t General Physiology
fuses with cell membrane. Now the waste products are                 ii. Degrade the toxic substances such as hydrogen
eliminated by exocytosis.                                                peroxide and other metabolic products by means
                                                                         of detoxification. A large number of peroxisomes
2. Degradation of worn-out organelles
                                                                         are present in the cells of liver, which is the major
The rough endoplasmic reticulum wraps itself around                      organ for detoxification. Hydrogen peroxide is
the worn-out organelles like mitochondria and form                       formed from poisons or alcohol, which enter the
the vacuoles called autophagosomes. One primary                          cell. Whenever hydrogen peroxide is produced
lysosome fuses with one autophagosome to form the                        in the cell, the peroxisomes are ruptured and
secondary lysosome. The enzymes in the secondary                         the oxidative enzymes are released. These
lysosome are activated. Now, these enzymes digest the                    oxidases destroy hydrogen peroxide and the
contents of autophagosome.                                               enzymes which are necessary for the production
3. Removal of excess secretory products in the cells                     of hydrogen peroxide
                                                                    iii. Form the major site of oxygen utilization in the
Lysosomes in the cells of the secretory glands remove
                                                                         cells
the excess secretory products by degrading the secretory
granules.                                                           iv. Accelerate gluconeogenesis from fats
                                                                     v. Degrade purine to uric acid
4. Secretory function – secretory lysosomes                        vi. Participate in the formation of myelin
Recently, lysosomes having secretory function                      viii. Play a role in the formation of bile acids.
called secretory lysosomes are found in some of the
cells, particularly in the cells of immune system. The           CENTROSOME AND CENTRIOLES
conventional lysosomes are modified into secretory
lysosomes by combining with secretory granules (which           Centrosome is the membrane-bound cellular organelle
contain the particular secretory product of the cell).          situated almost in the center of cell, close to nucleus.
    Examples of secretory lysosomes:                            It consists of two cylindrical structures called centrioles
       i. Lysosomes in the cytotoxic T lymphocytes and          which are made up of proteins. Centrioles are responsible
          natural killer (NK) cells secrete perforin and        for the movement of chromosomes during cell division.
          granzymes, which destroy both viral-infected
          cells and tumor cells. Perforin is a pore-forming      SECRETORY VESICLES
          protein that initiates cell death. Granzymes belong   Secretory vesicles are the organelles with limiting
          to the family of serine proteases (enzymes that       membrane and contain the secretory substances. These
          dislodge the peptide bonds of the proteins) and       vesicles are formed in the endoplasmic reticulum and
          cause the cell death by apoptosis                     are processed and packed in Golgi apparatus. Secretory
      ii. Secretory lysosomes of melanocytes secrete            vesicles are present throughout the cytoplasm. When
          melanin                                               necessary, these vesicles are ruptured and secretory
     iii. Secretory lysosomes of mast cells secrete             substances are released into the cytoplasm.
          serotonin, which is a vasoconstrictor substance
          and inflammatory mediator.                             MITOCHONDRION
                                                                4. Other functions
                                                                Other functions of mitochondria include storage of
                                                                calcium and detoxification of ammonia in liver.
                                                                 ORGANELLES WITHOUT
                                                                  LIMITING MEMBRANE
          FIGURE 1.6: Structure of mitochondrion                 RIBOSOMES
                                                                Ribosomes are the organelles without limiting mem-
in cristae are collectively known as respiratory chain or
                                                                brane. These organelles are granular and small dot-like
electron transport system.
                                                                structures with a diameter of 15 nm. Ribosomes are
Enzymes and other proteins of respiratory chain                 made up of 35% of proteins and 65% of ribonucleic acid
       i. Succinic dehydrogenase                                (RNA). RNA present in ribosomes is called ribosomal
      ii. Dihydronicotinamide adenine dinucleotide (NADH)       RNA (rRNA). Ribosomes are concerned with protein
          dehydrogenase                                         synthesis in the cell.
     iii. Cytochrome oxidase
                                                                Types of Ribosomes
     iv. Cytochrome C
      v. ATP synthase.                                          Ribosomes are of two types:
    Inner cavity of mitochondrion is filled with matrix which        i. Ribosomes that are attached to rough endo-
contains many enzymes. Mitochondrion moves freely in                    plasmic reticulum
the cytoplasm of the cell. It is capable of reproducing             ii. Free ribosomes that are distributed in the cyto-
itself. Mitochondrion contains its own deoxyribonucleic                 plasm.
acid (DNA), which is responsible for many enzymatic
actions. In fact, mitochondrion is the only organelle other
                                                                Functions of Ribosomes
than nucleus, which has its own DNA.
                                                                Ribosomes are called ‘protein factories’ because of
Functions of Mitochondrion                                      their role in the synthesis of proteins. Messenger RNA
1. Production of energy                                         (mRNA) carries the genetic code for protein synthesis
                                                                from nucleus to the ribosomes. The ribosomes, in turn
Mitochondrion is called the ‘power house’ or ‘power             arrange the amino acids into small units of proteins.
plant’ of the cell because it produces the energy required          Ribosomes attached to rough endoplasmic reticulum
for cellular functions. The energy is produced during the       are involved in the synthesis of proteins such as the
oxidation of digested food particles like proteins, carbo-
                                                                enzymatic proteins, hormonal proteins, lysosomal pro-
hydrates and lipids by the oxidative enzymes in cristae.
                                                                teins and the proteins of the cell membrane.
During the oxidative process, water and carbon dioxide
                                                                    Free ribosomes are responsible for the synthesis of
are produced with release of energy. The released ener-
gy is stored in mitochondria and used later for synthesis       proteins in hemoglobin, peroxisome and mitochondria.
of ATP.
                                                                 CYTOSKELETON
2. Synthesis of ATP
                                                                Cytoskeleton is the cellular organelle present throughout
The components of respiratory chain in mitochondrion            the cytoplasm. It determines the shape of the cell and gives
are responsible for the synthesis of ATP by utilizing the       support to the cell. It is a complex network of structures
energy by oxidative phosphorylation. ATP molecules
                                                                with varying sizes. In addition to determining the shape of
diffuse throughout the cell from mitochondrion. Whenever
                                                                the cell, it is also essential for the cellular movements and
energy is needed for cellular activity, the ATP molecules
are broken down.                                                the response of the cell to external stimuli.
                                                                    Cytoskeleton consists of three major protein
3. Apoptosis                                                    components:
Cytochrome C and second mitochondria-derived activator           1. Microtubule
of caspases (SMAC)/diablo secreted in mitochondria are           2. Intermediate filaments
involved in apoptosis (see below).                               3. Microfilaments.
  12    Section 1 t General Physiology
2. Intermediate Filaments
Intermediate filaments are the structures that form a                         FIGURE 1.7: Microtubule
network around the nucleus and extend to the periphery
of the cell. Diameter of each filament is about 10 nm. The
intermediate filaments are formed by ropelike polymers,
which are made up of fibrous proteins (Fig. 1.8).
Subclasses of intermediate filaments
Intermediate filaments are divided into five subclasses:
      i. Keratins (in epithelial cells)
     ii. Glial filaments (in astrocytes)
    iii. Neurofilaments (in nerve cells)
    iv. Vimentin (in many types of cells)
     v. Desmin (in muscle fibers).                                       FIGURE 1.8: Intermediate filament
Functions of intermediate filaments
Intermediate filaments help to maintain the shape of the
cell. These filaments also connect the adjacent cells
through desmosomes.
3. Microfilaments
Microfilaments are long and fine threadlike structures
with a diameter of about 3 to 6 nm. These filaments are
made up of non-tubular contractile proteins called actin
and myosin. Actin is more abundant than myosin.                        FIGURE 1.9: Microfilament of ectoplasm
                                                                                                Chapter 1 t Cell      13
    Nucleus is present in all the cells in the body except    packing unit of chromatin called nucleosome. Nucleo-
the red blood cells. The cells with nucleus are called        somes are packed together tightly with the help of a
eukaryotes and those without nucleus are known as             histone molecule to form a chromatin fiber.
prokaryotes. Presence of nucleus is necessary for cell            Just before cell division, the chromatin condenses to
division.                                                     form chromosome.
    Most of the cells have only one nucleus (uninucleated
cells). Few types of cells like skeletal muscle cells have    Chromosomes
many nuclei (multinucleated cells). Generally, the
nucleus is located in the center of the cell. It is mostly    Chromosome is the rod-shaped nuclear structure
spherical in shape. However, the shape and situation of       that carries a complete blueprint of all the hereditary
nucleus vary in some cells.                                   characteristics of that species. A chromosome is formed
                                                              from a single DNA molecule coiled around histone
 STRUCTURE OF NUCLEUS                                        molecules. Each DNA contains many genes.
                                                                  Normally, the chromosomes are not visible in the
Nucleus is covered by a membrane called nuclear mem-          nucleus under microscope. Only during cell division,
brane and contains many components. Major components          the chromosomes are visible under microscope. This is
of nucleus are nucleoplasm, chromatin and nucleolus.          because DNA becomes more tightly packed just before
                                                              cell division, which makes the chromosome visible
Nuclear Membrane                                              during cell division.
Nuclear membrane is double layered and porous in                  All the dividing cells of the body except reproductive
nature. This allows the nucleoplasm to communicate with       cells contain 23 pairs of chromosomes. Each pair consists
the cytoplasm. The outer layer of nuclear membrane is         of one chromosome inherited from mother and one from
continuous with the membrane of endoplasmic reticulum.        father. The cells with 23 pairs of chromosomes are called
The space between the two layers of nuclear membrane          diploid cells. The reproductive cells called gametes or
is continuous with the lumen of endoplasmic reticulum.        sex cells contain only 23 single chromosomes. These
    Pores of the nuclear membrane are guarded (lined)         cells are called haploid cells.
by protein molecules. Diameter of the pores is about
80 to 100 nm. However, it is decreased to about 7 to          Nucleolus
9 nm because of the attachment of protein molecules
                                                              Nucleolus is a small, round granular structure of the
with the periphery of the pores. Exchange of materials
                                                              nucleus. Each nucleus contains one or more nucleoli.
between nucleoplasm and cytoplasm occurs through
                                                              The nucleolus contains RNA and some proteins, which
these pores.
                                                              are similar to those found in ribosomes. The RNA is
                                                              synthesized by five different pairs of chromosomes and
Nucleoplasm
                                                              stored in the nucleolus. Later, it is condensed to form
Nucleoplasm is a highly viscous fluid that forms the          the subunits of ribosomes. All the subunits formed in
ground substance of the nucleus. It is similar to cytoplasm   the nucleolus are transported to cytoplasm through the
present outside the nucleus.                                  pores of nuclear membrane. In the cytoplasm, these
    Nucleoplasm surrounds chromatin and nucleolus.            subunits fuse to form ribosomes, which play an essential
It contains dense fibrillar network of proteins called the    role in the formation of proteins.
nuclear matrix and many substances such as nucleotides
and enzymes. The nuclear matrix forms the structural           FUNCTIONS OF NUCLEUS
framework for organizing chromatin. The soluble liquid
part of nucleoplasm is known as nuclear hyaloplasm.           Major functions of nucleus are the control of cellular
                                                              activities and storage of hereditary material. Several
                                                              processes are involved in the nuclear functions.
Chromatin
                                                                  Functions of nucleus:
Chromatin is a thread-like material made up of large           1. Control of all the cell activities that include metabolism,
molecules of DNA. The DNA molecules are compactly                  protein synthesis, growth and reproduction (cell
packed with the help of a specialized basic protein                division)
called histone. So, chromatin is referred as DNA-histone       2. Synthesis of RNA
complex. It forms the major bulk of nuclear material.          3. Formation of subunits of ribosomes
    DNA is a double helix which wraps around central           4. Sending genetic instruction to the cytoplasm for
core of eight histone molecules to form the fundamental            protein synthesis through messenger RNA (mRNA)
   14   Section 1 t General Physiology
 5. Control of the cell division through genes                 from amino acids. It is like a book that contains the
 6. Storage of hereditary information (in genes)               information necessary for protein synthesis. Gene is
    and transformation of this information from one            considered as the basic hereditary unit of the cell.
    generation of the species to the next.                         In the nucleotide of DNA, three of the successive
                                                               base pairs are together called a triplet or a codon. Each
 DEOXYRIBONUCLEIC ACID                                        codon codes or forms code word (information) for one
                                                               amino acid. There are 20 amino acids and there is
Deoxyribonucleic acid (DNA) is a nucleic acid that carries
the genetic information to the offspring of an organism.       separate code for each amino acid. For example, the
DNA forms the chemical basis of hereditary characters.         triplet CCA is the code for glycine and GGC is the code
It contains the instruction for the synthesis of proteins in   for proline.
the ribosomes. Gene is a part of a DNA molecule.                    Thus, each gene forms the code word for a particular
    DNA is present in the nucleus (chromosome)                 protein to be synthesized in ribosome (outside the
and mitochondria of the cell. The DNA present in the           nucleus) from amino acids.
nucleus is responsible for the formation of RNA. RNA
regulates the synthesis of proteins by ribosomes. DNA           GENETIC DISORDERS
in mitochondria is called non-chromosomal DNA.
                                                               A genetic disorder is a disorder that occurs because
                                                               of the abnormalities in an individual’s genetic material
 STRUCTURE OF DNA
                                                               (genome). Genetic disorders are either hereditary dis
DNA is a doublestranded complex nucleic acid. It              orders or due to defect in genes.
is formed by deoxyribose, phosphoric acid and four
types of bases. Each DNA molecule consists of two              Causes of Gene Disorders
polynucleotide chains, which are twisted around one
                                                               Genetic disorders occur due to two causes:
another in the form of a double helix. The two chains are
                                                                1. Genetic variation: Presence of a different form of
formed by the sugar deoxyribose and phosphate. These
                                                                   gene
two substances form the backbone of DNA molecule.
                                                                2. Genetic mutation: Generally, mutation means an
Both chains of DNA are connected with each other by
some organic bases (Fig. 1.10).                                    alteration or a change in nature, form, or quality.
    Each chain of DNA molecule consists of many                    Genetic mutation refers to change of the DNA
nucleotides. Each nucleotide is formed by:                         sequence within a gene or chromosome of an
 1. Deoxyribose – sugar                                            organism, which results in the creation of a new
 2. Phosphate                                                      character.
 3. One of the following organic (nitrogenous) bases:
     Purines       – Adenine (A)                               Classification of Genetic Disorders
                   – Guanine (G)                               Genetic disorders are classified into four types:
     Pyrimidines – Thymine (T)                                  1. Single gene disorders
                   – Cytosine (C)                               2. Multifactorial genetic disorders
    The strands of DNA are arranged in such a way that          3. Chromosomal disorders
both are bound by specific pairs of bases. The adenine          4. Mitochondrial DNA disorders.
of one strand binds specifically with thymine of opposite
strand. Similarly, the cytosine of one strand binds with       1. Single Gene Disorders
guanine of the other strand.
                                                               Single gene disorders or Mendelian or monogenic
    DNA forms the component of chromosomes, which
                                                               disorders occur because of variation or mutation in one
carries the hereditary information. The hereditary infor-
                                                               single gene. Examples include sickle cell anemia and
mation that is encoded in DNA is called genome. Each
                                                               Huntington’s disease.
DNA molecule is divided into discrete units called
genes.                                                         2. Multifactorial Genetic Disorders
                                                               Multifactorial genetic disorders or polygenic disorders
 GENE
                                                               are caused by combination of environmental factors and
Gene is a portion of DNA molecule that contains the            mutations in multiple genes. Examples are coronary heart
message or code for the synthesis of a specific protein        disease, Alzheimer’s disease, arthritis and diabetes.
                                                                                             Chapter 1 t Cell     15
     FIGURE 1.10: Structure of DNA. A. Double helical structure of DNA; B. Magnified view of the components of DNA.
                   A = Adenine, C = Cytocine, G= Guanine, P = Phosphate, S = Sugar, T = Thymine.
from cytokines. Growth factors act on the cells of the           Functional Significance of Apoptosis
growing tissues. But cytokines are concerned with the
                                                                 The purpose of apoptosis is to remove unwanted cells
cells of immune system and hemopoietic cells.
                                                                 without causing any stress or damage to the neighboring
    Many growth factors are identified. The known growth
                                                                 cells. The functional significance of apoptosis:
factors are:
                                                                  1. Plays a vital role in cellular homeostasis. About
  1. Plateletderived growth factor – PDGF (Chapter 18)
                                                                      10 million cells are produced everyday in human
  2. Colony stimulating factors – CSF (Chapter 16)
                                                                      body by mitosis. An equal number of cells die by
  3. Nerve growth factors – NGF (Chapter 134)
                                                                      apoptosis. This helps in cellular homeostasis
  4. Neurotropins (Chapter 134)
                                                                  2. Useful for removal of a cell that is damaged beyond
  5. Erythropoietin (Chapter 10)
                                                                      repair by a virus or a toxin
  6. Thrombopoietin (Chapter 18)
                                                                  3. An essential event during the development and in
  7. Insulinlike growth factors – IGF (Chapter 66)
                                                                      adult stage.
  8. Epidermal growth factor – present in keratinocytes
     and fibroblasts. It inhibits growth of hair follicles and     Examples:
     cancer cells
                                                                       i. A large number of neurons are produced during
  9. Basic fibroblast growth factor – present in blood
                                                                          the development of central nervous system.
     vessels. It is concerned with the formation of new
                                                                          But up to 50% of the neurons are removed by
     blood vessels
10. Myostatin – present in skeletal muscle fibers. It                     apoptosis during the formation of synapses
     controls skeletal muscle growth                                      between neurons
11. Transforming growth factors (TGF) – present in                    ii. Apoptosis is responsible for the removal of
     transforming cells (cells undergoing differentiation)                tissues of webs between fingers and toes during
     and in large quantities in tumors and cancerous                      developmental stage in fetus
     tissue. TGF is of two types:                                    iii. It is necessary for regression and disappearance
      i. TGFα secreted in brain, keratinocytes and                       of duct systems during sex differentiation in fetus
         macrophages. It is concerned with growth of                      (Chapter 74)
         epithelial cells and wound healing                          iv. The cell that looses the contact with neighboring
     ii. TGFβ secreted by hepatic cells, T lymphocytes,                  cells or basal lamina in the epithelial tissue dies
         B lymphocytes, macrophages and mast cells.                       by apoptosis. This is essential for the death of old
         When the liver attains the maximum size in                       enterocytes that shed into the lumen of intestinal
         adults, it controls liver growth by inhibiting pro-              glands (Chapter 41)
         liferation of hepatic cells. TGFβ also causes               v. It plays an important role in the cyclic sloughing
         immunosuppression.                                               of the inner layer of endometrium, resulting in
                                                                          menstruation (Chapter 80)
 CELL DEATH                                                         vi. Apoptosis removes the autoaggressive T cells
                                                                          and prevents autoimmune diseases.
Cell death occurs by two distinct processes:
 1. Apoptosis
 2. Necrosis.                                                    Activation of Apoptosis
                                                                 Apoptosis is activated by either withdrawal of positive
 APOPTOSIS                                                      signals (survival factors) or arrival of negative signals.
Apoptosis is defined as the natural or programed death           Withdrawal of positive signals
of the cell under genetic control. Originally, apoptosis
refers to the process by which the leaves fall from trees        Positive signals are the signals which are necessary for
in autumn (In Greek, apoptosis means ‘falling leaves’).          the long-time survival of most of the cells. The positive
It is also called ‘cell suicide’ since the genes of the cell     signals are continuously produced by other cells or
play a major role in the death.                                  some chemical stimulants. Best examples of chemical
     This type of programmed cell death is a normal              stimulants are:
phenomenon and it is essential for normal development                  i. Nerve growth factors (for neurons)
of the body. In contrast to necrosis, apoptosis usually               ii. Interleukin-2 (for cells like lymphocytes).
does not produce inflammatory reactions in the                       The absence or withdrawal of the positive signals
neighboring tissues.                                             activates apoptosis.
   18   Section 1 t General Physiology
 2. Fluid accumulation in the cell                                mellitus by cell replacement technique. But, ethical
 3. Fat infiltration into the cell                                issues arise because the embryo has to be destroyed to
 4. Calcification of cellular organelles.                         collect the stem cells.
                                                                  Stem cells from umbilical cord blood
 CELL AGING
                                                                  Stem cells in umbilical cord blood are collected from
Cell aging is the gradual structural and functional               the placenta or umbilical cord. Use of these stem cells
changes in the cells that occur over the passage of time.         for research and therapeutic purposes does not create
It is now suggested that cell aging is due to damage              any ethical issue because it does not endanger the life
of cellular substances like DNA, RNA, proteins and                of the fetus or newborn. Because of vitality and easy
lipids, etc. when the cell becomes old. When more                 availability, the umbilical cord blood stem cells are
cellular substances are damaged, the cellular function            becoming a potent resource for transplant therapies.
decreases. This causes deterioration of tissues, organs           Nowadays, these stem cells are used to treat about 70
or parts of the body. Finally, the health of the body starts      diseases and are used in many transplants worldwide.
declining and this leads to death. So, the cell aging
determines the health and life span of the body.                  2. Adult Stem Cells
                                                                  Embryonic stem cells do not disappear after birth. But
 STEM CELLS                                                      remain in the body as adult stem cells and play a role
                                                                  in repair of damaged tissues. However, their number
Stem cells are the primary cells capable of reforming
                                                                  becomes less. Adult stem cells are the undifferentiated
themselves through mitotic division and differentiating
                                                                  multipotent progenitor cells found in growing children
into specialized cells. These cells serve as repair               and adults. These are also known as somatic stem cells
system of the body and are present in all multicellular           and are found everywhere in the body. These cells are
organisms.                                                        capable of dividing and reforming the dying cells and
                                                                  regenerating the damaged tissues. So, these stem cells
 TYPES OF STEM CELLS                                             can also be used for research and therapeutic purposes.
                                                                      Adult stem cells are collected from bone marrow.
Stem cells are of two types:
                                                                  Two types of stem cells are present in bone marrow:
 1. Embryonic stem cells derived from embryo                            i. Hemopoietic stem cells, which give rise to blood
 2. Adult stem cells derived from adults.                                  cells (Chapter 10)
                                                                       ii. Bone marrow stromal cells, which can differ-
1. Embryonic Stem Cells                                                    entiate into cardiac and skeletal muscle cells.
Embryonic stem cells are derived from the inner cell
mass of a blastocyst which is an early stage of embryo.            ADVANTAGES OF STEM CELLS
It takes about 4 to 5 days after fertilization to reach           Adult stem cells from bone marrow are used in bone
the blastocyst stage and it has about 30 to 50 cells.             marrow transplant to treat leukemia and other blood
Embryonic stem cells have two important qualities:                disorders since 30 years. Recently, it is known that
      i. Self-renewal capacity                                    these stem cells can develop into nerve cells, liver cells,
     ii. Pluripotent nature, i.e. these cells are capable of      skeletal muscle cells and cardiac muscle cells.
         differentiating into all types of cells in ectodermal,      Recent discoveries also reveal that the stem cells
                                                                  are present in several tissues which include blood, blood
         endodermal and mesodermal layers.
                                                                  vessels, skeletal muscle, liver, skin and brain. It is also
    Because of these two qualities, the embryonic stem            found that these cells are capable of differentiating into
cells can be used therapeutically for regeneration or             multiple cell types. So, the cell-based therapy using
replacement of diseased or destroyed tissues. In fact,            stem cells may be possible to treat many diseases
embryonic pluripotent stem cells are now cultured and             such as heart diseases, diabetes, Parkinson’s disease,
lot of research is going on to explore the possibility of         Alzheimer’s disease, spinal cord injury, stroke and
using these cells in curing the disorders like diabetes           rheumatoid arthritis.