B.Pharmacy-Ist sem, Unit-I, Chapter-II

1. P r e s e n t e d b y : A b h i s h e k D a b ra ( A s s t . P r o f. )
B. PHARMACY-IST SEMESTER,
CHAPTER-II
CELLULAR LEVEL OF ORGANIZATION
Guru Gobind Singh College of Pharmacy,
Yamunanagar

3. INTRODUCTION
• The cell is the basic unit of structure and function in living
things.
• Cells vary in their shape size, and arrangements but all cells
have similar components, each with a particular function.
• Consist of plasma membrane enclosing a number of organelles
suspended in a watery fluid called cytosol (cytoplasm).
• Some of the 100 trillion of cells make up human body.
• The diameter range from 7.5 micrometer (RBC) to 150 mm
(ovum).

4. INTRODUCTION
- Cell is defined as the fundamental living unit of any organism.
- Cell is important to produce energy for metabolism (all chemical
reactions within a cell)
- Cell can mutate (change genetically) as a result of accidental
changes in its genetic material (DNA).
- Cytology: the study of the structure and functions of cells.
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5. ahmad ata 5

6. CELL STRUCTURE
1) The Cell (Plasma) Membrane:
• The cell membrane is a thin, dynamic membrane that
encloses the cell and controls what enters and leaves the
cell.
• Fluid Mosaic Model
composed of a double layer (bilayer) of phospholipid
molecules with many protein molecules embedded
within it;
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7. PLASMA MEMBRANE
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8. FUNCTION OF PLASMA MEMBRANE
• Serves as boundary of the cell.
• Serve as markers that identify the cells.
• Play significant role in transportation.
• Cell recognition proteins-allow cell to recognize other cells.

9. MEMBRANE PROTEINS
• Some membrane proteins have carbohydrates attached to
them, forming glycoproteins that act as identification
markers
• Some membrane proteins are receptors that react to
specific chemicals, sometimes permitting a process called
signal transduction

10. CYTOPLASM
• Is a gel-like matrix of water, enzymes, nutrients, wastes, and
gases and contains cell structures (organelles).
• Fluid around the organelles called cytosol.
• Most of the cells metabolic reactions occur in the cytoplasm.

11. 1) ENDOPLASMIC RETICULUM
It is an extensive series of interconnected parallel membranes canals, that is
continuous with the nuclear membrane;
Two types:
1. Smooth Endoplasmic Reticulum (RER):
ER studded with ribosomes;
Function = protein synthesis and intracellular transportation of molecules ;
2. Rough Endoplasmic Reticulum (SER):
lacks ribosomes;
Function = lipid & cholesterol synthesis, stores calcium, detoxification of some
drugs.

12. 2) RIBOSOMES
• Every cell contains thousand of ribosome's and many
of them attached to the RER.
• Each ribosome is non-membranous structure, made
of two pieces large unit and small unit and each
subunit composed of rRNA.
• Function: protein synthesis
• Protein released from the ER are not mature, need
further processing in Golgi complex before they are
able to perform their function within or outside the
cell.

13. 3) GOLGI APPARATUS
1. flattened membranous sacs (cisternae).
2. arranged in stacks ("stack of pancakes") associated with
many vesicles (membrane bound sacs containing proteins);
3. Function = modification, packaging, and transport of
proteins;
4. Encloses digestive enyzymes into membranes to form
lysosomes.

14. 4) LYSOSOMES
1. spherical membranous sacs containing digestive
enzymes;
2. "suicide bags" which destroy anything the cell no longer
wants or needs.
3. Autolysis is the process by which worn cell parts are
digested by autophagy.

15. 5) PEROXISOMES:
• 1. membranous sacs containing oxidase enzymes;
• 2. Function = detoxification of harmful or toxic substances
(i.e. alcohol, formaldehyde, oxygen free radicals);
• H2O2 (peroxide) ----> water

16. 6. MITOCHONDRIA
• 1. kidney-shaped
organelle whose inner
membrane is folded into
shelf-like partitions called
cristae;
• 2. "Powerhouse" of the
cell = site of cellular
respiration where energy is
released from glucose.
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17. 7. NUCLEUS
the central core, control center or
"brain" of the cell.
1. the largest organelle of the cell;
2. filled with nucleoplasm;
• Nuclear Membrane (or nuclear envelope) is a double membrane that
separates the contents of the nucleus from the cytoplasm;
• At various point, these two membranes fuse = nuclear pore.
• The nuclear membrane is "selectively permeable"; pores serve as
sites where mRNA can pass out of the nucleus during protein
synthesis, and how ribosomes exit the nucleus.

18. NUCLEOLUS
• Nucleolus (s) = a spherical body within the nucleus;
• composed of RNA and proteins;
• Function = synthesis of ribosomes.

19. 8. CYTOSKELETON :
• Consist of microfilaments and microtubules
• Is a network of fibers extending throughout the cytoplasm
• Fibers appear to support the endoplasmic reticulum,
mitochondria, and “free” ribosomes
Functions:
• Gives mechanical support to the cell
• Is involved in cell motility, which utilizes motor proteins
• Rod like pieces that provide support and allow movement and
mechanisms that can move the cell or its parts

20. Components of cytoskeleton:
1) Microfilaments
 Solid rods of globular proteins.
 Important component of cytoskeleton which offers support to
cell structure.
 Microfilaments can slide past each other, causing shortening of
the cell
2) intermediate Microfilaments
Intermediate filaments are twisted protein strands slightly
thicker than microfilaments; they form much of the
supporting framework in many types of cells

21. COMPONENTS OF CYTOSKELETON:
3) MICROTUBULES
• Shape the cell
• Guide movement of organelles (their function is to move
things around in the cell)
• Help separate the chromosome copies in dividing cells

22. CENTROSOMES AND CENTRIOLES
• An area of the cytoplasm near the nucleus that coordinates
the building and breaking of microtubules in the cell
• Its considered to be a “microtubule-organizing center”
• Plays an important role during cell division
• Contains a pair of centrioles

23. COMPONENTS OF CYTOSKELETON:
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Centrioles
 Self-replicating
 Made of bundles of
microtubules.
 Help in organizing cell
division.

24. CELL MEMBRANE SURFACE MODIFICATIONS
1.Cilia / Cilium
a. short, hair-like cellular extensions (eyelashes);
b. help move substances through passageways;
c. located in lining of respiratory tract & fallopian tube.
2.Flagella
a. tail-like projection;
b. only one per cell in humans;
c. aids in cell locomotion;
d. sperm cell.
3.Microvilli:
a. small finger-like extensions of the external surface of the cell membrane;
b. Function = to increase surface area.
c. located in the lining of the digestive tract.

25. FUNCTION OF CELL
1. Structure and Support:
Like a classroom is made of bricks, every organism is made of cells.
While some cells such as the cytoskeleton, bone cells and
microtubules are specifically meant for structural support, all cells
generally provide the structural basis of all organisms. For instance,
skin is made up of a number of skin cells.
2. Growth:
In complex organisms, tissues grow by simple multiplication of cells.
This takes place through the process of mitosis in which the parent
cell breaks down to form two daughter cells identical to it. Mitosis is
also the process through which simpler organisms reproduce and give
rise to new organisms.

26. FUNCTION OF CELL
3. Transport:
 Cells import nutrients to use in the various chemical processes that go on
inside them. These processes produce waste a cell needs to get rid of.
 Small molecules such as oxygen, carbon dioxide and ethanol get across the
cell membrane through the process of simple diffusion, which is regulated
with a concentration gradient across the cell membrane. This is known as
passive transport.
 However, larger molecules, such as proteins and polysaccharides, go in
and out of a cell through the process of active transport in which the cell
uses vesicles to excrete or absorb larger molecules.
4. Energy Production:
An organism's survival depends upon the thousands of chemical reactions
that cells carry out relentlessly. For these reactions, cells require energy.
Most plants get this energy through the process of photosynthesis whereas
respiration is the mechanism that provides energy to animal cells

27. FUNCTION OF CELL
5. Metabolism:
• Metabolism includes all the chemical reactions that take place inside an
organism to keep it alive. These reactions can be catabolic or anabolic. The
process of energy production by breaking down molecules (glucose) is
known as catabolism. Anabolic reactions, on the other hand, use energy to
make bigger substances from simpler ones.
6. Reproduction:
• Reproduction is vital for the survival of a species. A cell helps in
reproduction through the processes of mitosis (in more evolved
organisms) and meiosis. In mitosis cells simply divide to form new cells.
This is termed as asexual reproduction.
• Meiosis takes place in gametes or reproductive cells in which there is a
mixing of genetic information. This causes daughter cells to be genetically
different from the parent cells. Meiosis is a part of sexual reproduction

28. FUNCTION OF CELL
7. Motility:
Different cells exhibit different types of motility. In general the term motility
can refer to movement of some components of the cell or to the movement
of the whole cell e.g. within a fluid. Eukaryotic cells e.g. plant cells and
animal cells move via the actions of flexible cilia or flagella.
8. Secretion :
Some of the cells are secretory in nature. They form glands and secrete
something important ex; pancreatic cells which secrete insulin and glucagon
which maintain the level of glucose in blood , salivary gland secrete salivary
amylase which helps in digestion starch, sebaceous gland secrete oil on the
skin which provide moisture to skin and protects from dryness of skin etc.
They are found in all secretory organs
9. Storage:
Some of the cells help in storage of fat like adipose cell specially in palms,
feet and bums which help to reduce friction to the body. Some of the cells
store calcium in the form of granules.

29. FUNCTION OF CELL
10. Immunity
• White blood cells and lymphocytes maintain the defense mechanism of
the body. These cells produces antibody in the presence of any foreign
particles in the body.

31. Transport across cell membrane
• The plasma membrane is a selectively permeable barrier
between the cell and the extracellular environment.
• Its permeability properties ensure that essential molecules such
as glucose, amino acids, and lipids readily enter the cell,
metabolic intermediates remain in the cell, and waste
compounds leave the cell.
• In other words, plasma membranes are selectively permeable.

33. Type of transport processes
• Two type of transport processes:
Transporting substances across the plasma membrane can require
that the cell use some of its energy. If energy is used, the transport
is called active transport.
If molecules can pass through the plasma membrane without using
energy, the molecules are using passive transport.
1. Passive transport:
i. Diffusion
ii. Osmosis
iii. Filtration
2. Active transport:
i. Primary active transport
ii. Secondary active transport

34. 1. Passive Transport
 Substances move down its concentration or electrical gradient to
cross the membrane using its own kinetic energy.
 Kinetic energy is intrinsic to the particles that are moving.
 No input of energy from the cell.
a. Diffusion:
i. Diffusion is a passive process of transport. A single substance
tends to move from an area of high concentration to an area of
low concentration until the concentration is equal across a
space.
ii. Materials move within the cell‘s cytosol by diffusion, and certain
materials move through the plasma membrane by diffusion.
Diffusion expends no energy

36. b. Osmosis:
i. It is a net movement of solvent through a selectively permeable
membrane. In living systems, the solvent is water, which moves
by osmosis across plasma membranes from an area of higher
water concentration to lower concentration.
ii. In other words water move through a selectively permeable
membrane from an area of lower solute concentration to an
area of higher solute concentration.
iii. Water molecules pass through a plasma membrane in two ways
By moving through the lipid bilayer and by moving through
aquaporins (integral membrane proteins that function as water
channels).

38. c. Filtration:
i. The last form of passive transport is used most often in the
capillaries. Capillaries are so thin (their membranes are only
one cell thick) that diffusion easily takes place through them.
But remember that animals have a blood pressure.
ii. The pressure at which the blood flows through the capillaries
have enough force to push water and small solutes that have
dissolved in the water right through the capillary membrane.
iii. So, in essence, the capillary membrane acts as filter paper,
allowing fluid to surround the body’s cells and keeping large
molecules from getting into the tissue fluid

40. 2. Active transport:
i. It is the movement of dissolved molecules into or out of a cell
through the cell membrane, from a region of lower
concentration to a region of higher concentration. The particles
move against the concentration gradient, using energy released
during respiration.
a) Primary active transport
b) Secondary active transport

42. a) Primary active transport
• It is also called direct active transport, directly uses chemical
energy (such as from adenosine triphosphate or ATP in case of
cell membrane) to transport all species of solutes across a
membrane against their concentration gradient.
• Uptake of glucose in the human intestines is an example of
primary active transport. Other sources of energy for primary
active transport are redox energy (chemical reaction such as
oxidation and reduction) and photon energy (light)

43. b) Secondary active transport
• This allows one solute to move downhill (along its
electrochemical potential gradient) in order to yield enough
entropic energy to drive the transport of the other solute uphill
(from a low concentration region to a high one).
• This is also known as coupled transport, as opposed to non-
coupled or uniport transport where transport of a single
component is facilitated.
• There are two main forms of coupled transport: antiport and
symport. In antiport two species of ion or other solutes are
pumped in opposite directions across a membrane and in
symport transport two species move in the same direction.

46. Cell junction
• There are 4 principle types of junctions between animal cells.
These junctions involve proteins that act as rivets or bolts to bind
neighboring cells together.
• These junctions may occur wherever neighboring cells contact
one another and these contact areas are often highly folded to
form inter-digitating processes that interlock and help bind the
cells more strongly.
i. Tight junction
ii. Adherens junction
iii. Desmosomes
iv. Gap junction

47. i. Tight junction
 Tight junctions seal epithelial layers to prevent materials leaking
across the epithelium between the cells (which would be non-
selective) – instead materials must pass through the cells and this
transport can be regulated.
 E.g. endocytosis may occur at the apical membrane and
exocytosis at the basolateral. They also divide the epithelial cell
membrane into apical (luminal) and basolateral membranes and
keep the proteins of these membrane regions separate (red and
green spheres).

49. ii. Adherens Junction
 Adherens junctions bond cells together strongly, for example they
bond cardiac muscle cells together, to stop the tissue tearing
when the heart contracts.

50. iii. Desmosomes
Desmosomes are
similar in some
respects to focal
adhesions of the
adherens type
and also contain
cadherins, but
they link in to the
intermediate
filaments of the
cytoskeleton

51. iv. Gap Junction
 These are formed from proteins in the cell membranes that form
hollow tubes through which small molecules and ions (with a
molecular mass below 1000) electrochemical signals, such as
Ca2+ (a second messenger) or Na+ can be delivered from one cell
to its neighbours.
 If you touch a single cell in an epithelial sheet, then not only that
cell will respond, but also its neighbours, as an electrical signal
passes from the stimulated cell to the neighbouring cells via the
gap junctions.

53.  Gap junctions are extremely important for coordinating cells in a
tissue and tissues requiring precise coordination have lots of gap
junctions, for example, cardiac muscle, which must beat in
synchrony, or the smooth muscle of the uterus wall ready for
child-birth.
 They also occur in certain locations in the nervous system as
electrical synapses which are faster than chemical synapses, but
are bidirectional rather than unidirectional.
 Gap junctions allow cells to communicate rapidly with their
nearest neighbours.s

55. Forms of intracellular signaling
 Cell-cell signaling involves the transmission of a signal from a
sending cell to a receiving cell. However, not all sending and
receiving cells are next-door neighbors, nor do all cell pairs
exchange signals in the same way.
 There are four categories of chemical signaling found in
multicellular organisms:
i. Paracrine signaling
ii. Endocrine signaling
iii. Autocrine signaling
iv. Direct signaling across gap junctions.

57. i. Paracrine Signaling
• Signals that act locally between cells that are close together are
called paracrine signals. Paracrine signals move by diffusion
through the extracellular matrix.
• These types of signals usually elicit quick responses that last only
a short amount of time. In order to keep the response localized,
paracrine ligand molecules are normally quickly degraded by
enzymes or removed by neighboring cells.
• Removing the signals will reestablish the concentration gradient
for the signal, allowing them to quickly diffuse through the
intracellular space if released again.

58. Paracrine
Signaling

59. ii. Endocrine Signaling
• Signals from distant cells are called endocrine signals; they
originate from endocrine cells.
• In the body, many endocrine cells are located in endocrine
glands, such as the thyroid gland, the hypothalamus, and the
pituitary gland.
• These types of signals usually produce a slower response, but
have a longer-lasting effect.
• The ligands released in endocrine signaling are called hormones,
signaling molecules that are produced in one part of the body,
but affect other body regions some distance away.
• Hormones travel the large distances between endocrine cells and
their target cells via the bloodstream, which is a relatively slow
way to move throughout the body.
• Because of their form of transport, hormones get diluted and are
present in low concentrations when they act on their target cells.

60. Endocrine Signaling

61. iii. Autocrine Signaling
• Autocrine signals are produced by signaling cells that can also
bind to the ligand that is released.
• This means the signaling cell and the target cell can be the same
or a similar cell (the prefix auto- means self, a reminder that the
signaling cell sends a signal to itself).
• This type of signaling often occurs during the early development
of an organism to ensure that cells develop into the correct
tissues and take on the proper function.
• Autocrine signaling also regulates pain sensation and
inflammatory responses. Further, if a cell is infected with a virus,
the cell can signal itself to undergo programmed cell death, killing
the virus in the process.

63. iv. Direct cell signaling across gap junction
• Gap junctions in animals and plasmodesmata in plants are
connections between the plasma membranes of neighboring
cells.
• These water-filled channels allow small signaling molecules,
called intracellular mediators, to diffuse between the two cells.
Small molecules, such as calcium ions (Ca2+), are able to move
between cells, but large molecules, like proteins and DNA, cannot
fit through the channels.
• The specificity of the channels ensures that the cells remain
independent, but can quickly and easily transmit signals. The
transfer of signaling molecules communicates the current state of
the cell that is directly next to the target cell; this allows a group
of cells to coordinate their response to a signal that only one of
them may have received

66. Cell Division
Actively dividing eukaryote cells pass through a series of stages
known collectively as the cell cycle: two gap phases (G1 and G2); an
S (for synthesis) phase, in which the genetic material is duplicated;
and an M phase, in which mitosis partitions the genetic material
and the cell divides.
Cell division is of two types:
1. Mitosis (in somatic cells)
2. Meiosis (In germ cells)

68. • G1 phase. Metabolic changes prepare the cell for division. At a
certain point - the restriction point - the cell is committed to
division and moves into the S phase.
• S phase. DNA synthesis replicates the genetic material. Each
chromosome now consists of two sister chromatids.
• G2 phase. Metabolic changes assemble the cytoplasmic materials
necessary for mitosis and cytokinesis.
• M phase. A nuclear division (mitosis) followed by a cell division
(cytokinesis).
The period between mitotic divisions - that is, G1, S and G2 - is
known as interphase.

69. 1. Mitosis:
• Mitosis is a form of eukaryotic cell division that produces two
daughter cells with the same genetic component as the parent
cell.
• Chromosomes replicated during the S phase are divided in such a
way as to ensure that each daughter cell receives a copy of every
chromosome. In actively dividing animal cells, the whole process
takes about one hour.
• The replicated chromosomes are attached to a 'mitotic
apparatus' that aligns them and then separates the sister
chromatids to produce an even partitioning of the genetic
material.
• This separation of the genetic material in a mitotic nuclear
division (or karyokinesis) is followed by a separation of the cell
cytoplasm in a cellular division (or cytokinesis) to produce two
daughter cells.

71. i. Prophase
• Prophase occupies over half of mitosis. The nuclear membrane
breaks down to form a number of small vesicles and the
nucleolus disintegrates.
• A structure known as the centrosome duplicates itself to form
two daughter centrosomes that migrate to opposite ends of the
cell.
• The centrosomes organise the production of microtubules that
form the spindle fibres that constitute the mitotic spindle.
• The chromosomes condense into compact structures. Each
replicated chromosome can now be seen to consist of two
identical chromatids (or sister chromatids) held together by a
structure known as the centromere.

72. ii. Prometaphase:
• The chromosomes, led by their centromeres, migrate to the
equatorial plane in the midline of cell - at right-angles to the axis
formed by the centrosomes.
• This region of the mitotic spindle is known as the metaphase
plate.
• The spindle fibres bind to a structure associated with the
centromere of each chromosome called a kinetochore. Individual
spindle fibres bind to a kinetochore structure on each side of the
centromere. The chromosomes continue to condense.
iii. Metaphase
• The chromosomes align themselves along the metaphase plate of
the spindle apparatus.

73. iv. Anaphase
• The shortest stage of mitosis. The centromeres divide, and the
sister chromatids of each chromosome are pulled apart - or
'disjoin' - and move to the opposite ends of the cell, pulled by
spindle fibres attached to the kinetochore regions.
• The separated sister chromatids are now referred to as daughter
chromosomes. (It is the alignment and separation in metaphase
and anaphase that is important in ensuring that each daughter
cell receives a copy of every chromosome).

74. v. Telophase
• The final stage of mitosis, and a reversal of many of the processes
observed during prophase.
• The nuclear membrane reforms around the chromosomes
grouped at either pole of the cell, the chromosomes uncoil and
become diffuse, and the spindle fibres disappear.
Cytokinesis
• The final cellular division to form two new cells. In plants a cell
plate forms along the line of the metaphase plate; in animals
there is a constriction of the cytoplasm.
• The cell then enters interphase - the interval between mitotic
divisions.

75. 2. Meiosis
• Meiosis is the form of eukaryotic cell division that produces
haploid sex cells or gametes (which contain a single copy of each
chromosome) from diploid cells (which contain two copies of
each chromosome).
• The process takes the form of one DNA replication followed by
two successive nuclear and cellular divisions (Meiosis I and
Meiosis II).
• As in mitosis,
• meiosis is preceded by a process of DNA replication that converts
each chromosome into two sister chromatids.

76. • In Meiosis I a special cell division reduces the cell from diploid to
haploid.
1. Prophase-I: The homologous chromosomes pair and exchange
DNA to form recombinant chromosomes.
• Prophase I is divided into five phases:
a. Leptotene: chromosomes start to condense.
b. Zygotene: homologous chromosomes become closely associated
(synapsis) to form pairs of chromosomes (bivalents) consisting of
four chromatids (tetrads).
c. Pachytene: crossing over between pairs of homologous
chromosomes to form chiasmata.
d. Diplotene: homologous chromosomes start to separate but
remain attached by chiasmata.
e. Diakinesis: homologous chromosomes continue to separate, and
chiasmata move to the ends of the chromosomes.

77. 2. Prometaphase-I:
Spindle apparatus formed, and chromosomes attached to spindle
fibres by kinetochores.
3. Metaphase-I:
Homologous pairs of chromosomes (bivalents) arranged as a double
row along the metaphase plate. The arrangement of the paired
chromosomes with respect to the poles of the spindle apparatus is
random along the metaphase plate.
4. Anaphase-I:
The homologous chromosomes in each bivalent are separated and
move to the opposite poles of the cell.
5. Telophase-I:
The chromosomes become diffuse and the nuclear membrane
reforms.

78. Cytokinesis:
The final cellular division to form two new cells, followed by
Meiosis-II. Meiosis-I is a reduction division: the original diploid cell
had two copies of each chromosome; the newly formed haploid
cells have one copy of each chromosome.

81. Meiosis-II
Meiosis II separates each chromosome into two chromatids. The
events of Meiosis II are analogous to those of a mitotic division,
although the number of chromosomes involved has been halved.
Meiosis generates genetic diversity through:
a. the exchange of genetic material between homologous
chromosomes during Meiosis I
b. the random alignment of maternal and paternal chromosomes in
Meiosis I
c. the random alignment of the sister chromatids at Meiosis II

85. General principle of cell communication
• Cell signaling is an intricate system of communication that
coordinates cell actions and regulates basic cellular activity. Cells
can sense and respond to their microenvironment based upon
their internal and external signals during development, tissue
repair, immunity, and normal tissue homeostasis.
• Cancer and autoimmune diseases are often caused by errors
during the information processing process. Understanding cell
signaling can lead to effective treatments for diseases, and it may
be possible, in theory, to generate artificial tissues.
• Chemical signals are typically used by cells to communicate.
Chemical signals made up of proteins and other molecules
produced by cells are frequently secreted into the extracellular
space by the cells sending them. They can then float over to
neighboring cells - like a message in a bottle.

86. The cell is able to generate an integrated response reflecting the
sum total of diverse signal input. The transducer mechanism can
be grouped into 5 major categories. Receptor falling in one
category also possess considerable structural homology and
belong to one super family of receptor
1. G-protein coupled receptor (GPCR’s)
2. Ion channel receptor
3. Transmembrane enzyme linked receptors
4. Transmembrane JAK-STAT binding reeptor
5. Receptor regulating gene expression (Transcription factors,
nuclear receptors)
Intracellular signaling pathway activation by
extracellular signaling molecule

87. 1. G-Protein Coupled Receptor
• These are a large family of cell membrane receptors which are
linked to the effector (enzyme/ channel/carrier protein) through
one or more GTPactivated proteins (G-proteins) for response
effectuation.
• All such receptors have a common pattern of structural
organization. The molecule has 7 α-helical membrane spanning
hydrophobic amino acid (AA) segments which run into 3
extracellular and 3 intracellular loops. The agonist binding site is
located somewhere between the helices on the extracellular
face, while another recognition site formed by cytosolic segments
binds the coupling G-protein.
• The G-proteins float in the membrane with their exposed domain
lying in the cytosol, and are heterotrimeric in composition (α, β
and γ subunits).

88. 3 major effective pathway
a) Adenylyl cyclase: cAMP Pathway
b) Phospholipase C: IP3/DAG Pathway
c) Channel regulation
Types of G-Protein
I. Gs: AC Activation/Calcium Channel activation
II. Gi: Adenylyl cyclase inhibition, K+ Channel opening
III. Go: calcium channel inhibition
IV. Gq: Phospholipase C activation

89. i. Adrenaline (Adr) binds to β-adrenergic receptor (β-R) on the cell surface inducing a
conformational change which permits interaction of the G-protein binding site with
the stimulatory G-protein (Gs).
ii. The activated α subunit of Gs now binds GTP (in place of GDP), and dissociates from
the βγ diamer as well as the receptor.
iii. The Gsα carrying bound GTP associates with and activates the enzyme adenylyl
cyclase (AC) located on the cytosolic side of the membrane: ATP is hydrolysed to
cAMP which then phosphorylates and thus activates cAMP dependent protein
kinase (PKA).
iv. The PKA in turn phosphorylates many functional proteins including troponin and
phospholamban, so that they interact with Ca2+, respectively resulting in increased
force of contraction and faster relaxation.
v. Calcium is made available by entry from outside (direct activation of myocardial
membrane Ca2+ channels by Gsα and through their phosphorylation by PKA) as
well as from intracellular stores.
vi. Action of acetylcholine (ACh) on muscarinic M2 receptor (M2-R), also located in the
myocardial membrane, similarly activates an inhibitory G-protein (Gi). The GTP
carrying active Giα subunit inhibits AC, and opposes its activation by Gsα. The βγ
diamer of Gi activates membrane K+ channels causing hyperpolarization which
depresses impulse generation.
a. cAMP pathway: Adenylyl cyclase

90. a. cAMP pathway: Adenylyl cyclase

91. b. Phospholipase C: IP3/DAG Pathway
i. The agonist, e.g. histamine binds to its H1 receptor (H1 R) and activates
the G-protein Gq. Its α subunit binds GTP in place of GDP, dissociates
from the receptor as well as from βγ diamer to activate membrane
bound PLcβ that hydrolyses phosphatidyl inositol 4, 5-bisphosphate
(PIP2), a membrane bound phospholipid.
ii. The products inositol 1, 4, 5-trisphosphate (IP3) and diacylglycerol (DAG)
act as second messengers. The primary action of IP3 is facilitation of
Ca2+ mobilization from intracellular organellar pools, while DAG in
conjunction with Ca2+ activates protein kinase C (PKc) which
phosphorylates and alters the activity of a number of functional and
structural proteins.
iii. Cytosolic Ca2+ is a veritable messenger: combines with calmodulin
(CAM) to activate myosin light chain kinase (MLCK) inducing contraction,
and another important regulator calcium-calmodulin protein kinase
(CCPK).
iv. Several other effectors are regulated by Ca2+ in a CAM dependent or
independent manner. Cytosolic Ca2+ is recycled by uptake into the
endoplasmic reticulum as well as effluxed by membrane Ca2+ pump.

92. b. Phospholipase C: IP3/DAG Pathway

93. 2. Ion channel receptor
• These cell surface receptors, also called ligand gated ion channels, enclose ion
selective channels (for Na+, K+, Ca2+ or Cl¯) within their molecules. Agonist
binding opens the channel and causes depolarization/hyperpolarization/
changes in cytosolic ionic composition, depending on the ion that flows
through.
a) Voltage-gated ion channel:
• Voltage-gated ion channels are a class of trans-membrane ion channels that
are activated by changes in electrical potential difference near the channel.
• These types of ion channels are especially critical in neurons, but are common
in many types of cells.
• They have a crucial role in excitable neuronal and muscle tissues, allowing a
rapid and coordinated depolarization in response to triggering voltage
change.
• Found along the axon and at the synapse, voltage-gated ion channels
directionally propagate electrical signals.
• They generally are composed of several subunits arranged in such a way that
there is a central pore through which ions can travel down their
electrochemical gradients.

94. Voltage-gated ion channel

95. a) ligand-gated ion channel:
• They are a group of trans-membrane ion channels that are opened or closed in
response to the binding of a chemical messenger (i.e., a ligand) such as a
neurotransmitter.
• The binding sites of endogenous ligands on LGICs protein complexes are normally
located on a different portion of the protein (an allosteric binding site) compared
to where the ion conduction pore is located.
• The direct link between ligand binding and opening or closing of the ion channel,
which is characteristic of ligand-gated ion channels, is contrasted with the indirect
function of metabotropic receptors, which use second messengers.
• The ion channel is regulated by a ligand and is usually very selective to one or
more ions like Na+, K+, Ca2+, or Cl-. Such receptors located at synapses, convert
the chemical signal of presynaptically released neurotransmitter directly and very
quickly into a postsynaptic electrical signal.

96. ligand-gated ion channel

97. 3. Enzyme linked receptors
• This class of receptors have a subunit with enzymatic property or
bind a JAK (Janus-Kinase) enzyme on activation. The agonist
binding site and the catalytic site lie respectively on the outer and
inner face of the plasma membrane (Fig. 4.8). These two domains
are interconnected through a single transmembrane stretch of
peptide chain.
There are two major subgroups of such receptors.
a. Those that have intrinsic enzymatic activity
b. Those that lack intrinsic enzymatic activity, but bind a JAK-STAT
kinase on activation.

98. a. Intrinsic enzyme receptors:
 Intrinsic tyrosine protein kinase receptor: On binding the peptide
hormone to the extracellular domains, the monomeric receptors
move laterally in the membrane and form diamers.
 Dimerization activates tyrosine-protein kinase (t-Pr-K) activity of
the intracellular domains so that they phosphorylate tyrosine (t)
residues on each other, as well as on several SH2 domain
substrate proteins (SH2-Pr).
 The phosphorylated substrate proteins then perform
downstream signaling function.

99. a. Intrinsic enzyme receptors

100. b. Trans-membrane JAK-STAT binding
• Intracellular domains of these receptors lack intrinsic protein
kinase activity
• Cytokines/hormones binding to the extracellular domain induce
receptor dimerization which activates the intracellular domain
to bind free moving JAK (Janus Kinase) molecule.
• The activated JAK phosphorylate tyrosine residue on the
receptor which then bind another protein STAT (signal
transducer and activator of transcription).
• Tyrosine residue of STAT also get phosphorylated by JAK.
• The phosphorylated STAT dimerize, dissociate from the receptor
and move to the nucleus to regulate transcription of target
genes.

101. b. Transmembrane JAK-STAT binding

102.  The glucocorticoid (G) penetrates the cell membrane and binds to the
glucocorticoid receptor (GR) protein that normally resides in the
cytoplasm in association with 3 other proteins viz, heat shock protein 90
(HSP90), HSP70 and immunophilin (IP).
 The GR has a steroid binding domain near the carboxy terminus and a
mid region DNA binding domain having two zinc fingers; each made up
of a loop of amino acid with chelated zinc ion.
 Binding of the steroid to GR dissociates the complexed protein (HSP90
etc) removing their inhibitory influence on it.
 A dimerization region that overlaps the steroid binding domain is
exposed, promoting dimerization of the occupied receptor.
 The steroid bound receptor diamer translocates to the nucleus and
interacts with specific DNA sequences called ‘glucocorticoid responsive
elements’ (GREs) within the regulatory region of appropriate genes.
 The expression of these genes is consequently altered resulting in
promotion (or suppression) of their transcription.
4. Receptor regulating gene-expression

103. 4. Receptor regulating gene-expression

104. References
1. Waugh A., Grant A., “ Ross and Wilson Anatomy & Physiology in health and illness,
Churchill Livingstone, 12th ed., 2014, Page no. 35-42.
2. Tripathi K.D., Essential of Medical pharmacology, JAYPEE Brothers Medical Publisher, 6th
ed., 2008, Page no. 45-52.