Chapter 1(A)

Topic 1: Basic Biochemistry

BC1.1 Describe the molecular and functional organization

of a cell and its subcellular components and composition
and functions of Biological membranes.

VIMS
Learning Objectives
Classify living cells
Describe molecular and functional organization of a cell and its
subcellular components
Describe structure and functions of cytoskeleton
 Classification Of Living Cells
 All organisms are grouped into one of three major domains: archaea,
bacteria and eukaryotes.
 Archaea and Bacteria (single-cell microorganism) can be distinguished
on genetic and biochemical grounds.
 Archaea lives in extreme environments: salt lakes hot springs, highly
acidic bogs, and the ocean depths. Archaea may be the most primitive
of the groups.
 Bacteria live in soils, surface waters, and the tissues of other living or
decaying organisms. Bacteria are classified as prokaryotes.
 Eukaryote include single cell organism such as yeast, fungi and
multicellular plants and animals.
Figure 1.1: Cell structure of eukaryotic and prokaryotic cell.
 What Are viruses?
 Viruses are not living organism in the sense that cells are. They are
incapable of replicate themselves outside their host cells and have
virtually no biochemical activities of their own.
 Viruses are supramolecular complexes of nucleic acid, either DNA or
RNA encapsulated in a protein coat, and in some instances,
surrounded by a membrane envelope.
 Viruses are not alive; they are not even cellular. Instead, they are
packaged bits of genetic material that can parasitize in order to
reproduce.
 Viruses infecting bacteria are called bacteriophages (“bacteria
eaters”): different viruses infect animal cells and plants cells.
 Molecular And Functional Organization
Of A Cell And Its Subcellular Components
A cell has three major components.

1. Plasma membrane (cell membrane)

2. Cytoplasm with its organelles

–– Endoplasmic reticulum
–– Golgi apparatus
–– Mitochondria
–– Lysosomes
–– Peroxisomes.

3. Nucleus
Cell Membrane (Plasma Membrane)
 Most membranes composed primarily of lipids and proteins.
 The basic structure of the cell membrane is a lipid bilayer (two layers
of lipids).
 Large globular protein molecules are interspreaded in this lipid
bilayer.
Figure 1.2: The basic organization of biological membrane.
The membrane is sometimes referred to as a fluid mosaic.
The membrane mosaic is fluid because most of the interactions
among its components are non-covalent, leaving individual lipid and
protein molecules free to move laterally in the plane of the
membrane.
Figure 1.3: The fluid mosaic model of cell membrane.
 The lipid of the membrane provides a barrier that obstructs the
movements of water and water-soluble substances from one cell
compartment to another.
 However, protein molecules in the membrane often do penetrate all
the way through the membrane, organized into actual pores, for
passage of specific substances through the membrane.
 Also many other membrane proteins are enzymes that catalyze
different types of chemical reactions.
The approximate composition of cell membrane is:
 Protein: 55%
 Phospholipids: 25%
 Cholesterol: 13%
 Other lipids: 4%
 Carbohydrate: 3%
Lipid of the membrane
 The basic lipid bilayer is composed of phospholipid molecules.
 One end of each phospholipid molecule (head group) is soluble in
water that is it is hydrophilic.
 The other end (tail group) is soluble only in fats; that is, it is
hydrophobic.
 The phosphate end of the phospholipid is hydrophilic and the free
fatty acid portion is hydrophobic.
A B
Figures 1.4A and B: Structure of phospholipid.
(A) A common glycerophospholipid;
(B) Diagrammatic representation of phospholipid.
The principle phospholipids in the membrane are:
 Glycerophospholipids:
• phosphatidylcholine,
• phosphatidylethanolamine, and
• phosphatidylserine
 Sphinogophospholipid: sphingomyelin.
 The lipid composition varies among different cell types, with
phosphatidylcholine being the major plasma membrane
phospholipid in most cell types.
 Plasma membrane for example, is enriched in cholesterol and
contains no detectable cardiolipin; mitochondrial membrane is very
low in cholesterol and sphingolipids but that contain cardiolipin.
Cholesterol
 The cholesterol molecules in the membrane are also lipid in
nature.
 Cholesterol, which is interspreaded between the
phospholipids, maintains membrane fluidity.
 Unsaturated fatty acid chains of the glycerophospholipids
bent into the cis conformation form a pocket for
cholesterol, which binds with its hydroxyl group in the
external hydrophilic region of the membrane and its
hydrophobic steroid nucleus in the hydrophobic membrane
core.
 The presence of cholesterol and the cis unsaturated fatty acids in the
membrane prevent the hydrophobic chains from packing too closely
together.
 The changes in membrane fluidity may affect proteins that span the
membrane (integral proteins), such as ion channels and receptors for
neurotransmitters involved conducting the nerve impulse.
Membrane Proteins
 The protein composition of membrane from different sources varies
even more widely than their lipid composition, reflecting functional
specialization.
 Two types of membrane proteins differ in their association with the
membrane.
 Most of the membrane proteins are glycoproteins.
Integral membrane proteins: Integral proteins that are protruding all
the way through the membrane. They are very firmly associated with
the lipid bilayer.
Peripheral membrane proteins: Peripheral proteins that are attached
only to one surface of the membrane and do not penetrate all the way
through.
 Peripheral protein molecules are often attached to the integral
proteins.
 They are associated with the membrane through electrostatic
interactions and hydrogen bonding with the hydrophilic domains of
integral proteins and with polar head groups of membrane lipids
Functions of membrane Proteins
 Integral membrane proteins function primarily as channels (pores)
through which water molecules and water soluble substances,
especially ions, can diffuse between extracellular and intracellular
fluids.
 Other integral proteins act as carrier proteins transporting
substances that otherwise could not penetrate the lipid bilayer.
 They can also serve as receptors for hormones and neurotransmitter.
 Integral proteins spanning the cell membrane provide a means of
conveying information about the environment to the cell interior.
 Peripheral proteins function almost entirely as enzymes or as
controllers of transport of substances through the cell membrane
“pores”.
Membrane carbohydrates
 Membrane carbohydrates occur in combination with proteins or lipids in
the form of glycoproteins or glycolipids.
 Some of the proteins and lipids on the external surface of the membrane
contain short chains of carbohydrate (oligosaccharides) that extent into
the aqueous medium.
 As well as many other carbohydrate compounds called
proteoglycans are loosely attached to the outer surface of the cell.
 Thus the entire outside surface of the cell often has a loose
carbohydrate coat called the glycocalaxy.
 Carbohydrate constitutes 2% to 10% of the weight of cell
membrane.
Functions of Membrane carbohydrates
 Many of the carbohydrates have a negative electrical charge, which
gives most cells an overall negative surface charge that repels other
negative objects and restricts the uptake of hydrophobic compounds.
 The glycocalaxy of some cell attaches to the glycocalaxy of other cells,
thus attaching cells to one another.
 Many carbohydrate act as hormone receptor such as insulin
 Some carbohydrate moieties involved into immune reactions.
Functions of Plasma Membrane
 The plasma membrane maintains the physical integrity of the cell by
preventing the contents of the cell from leaking into the outside fluid
environment and at the same time facilitating the entry of nutrients,
inorganic ions and most other charged or polar compounds from the
outside.
 The functions of the plasma membrane are coordinated by
specialized adhesion receptors called integrins. Integrins are integral
transmembrane proteins. Integrins represent important cell
receptors that regulate fundamental cellular process; such as
attachment, movement, growth and differentiation.
 Cytoplasm and its Organelles
Five important organelles that are suspended in the cytosol are.
1. Endoplasmic reticulum
2. Golgi apparatus
3. Mitochondria
4. Lysosomes
5. Peroxisomes
Endoplasmic Reticulum
 The endoplasmic reticulum (ER) is the interconnected folded network
of tubular structures in the cytoplasm.
 A portion of the endoplasmic reticulum has ribosomes bound to it,
which give it a rough appearance in contrast with smooth
endoplasmic reticulum which is devoid of ribosomes.
 Endoplasmic reticulum and Golgi apparatus are involved in formation
of other cellular organelles such as lysosomes and peroxisomes
 A B

Figures 1.5A and B: Structure of endoplasmic reticulum.

(A) Rough or granular endoplasmic reticulum; and
(B) Smooth or a granular endoplasmic reticulum.
Functions of Endoplasmic Reticulum
 The rough endoplasmic reticulum is the site for synthesis of proteins.
 The endoplasmic reticulum also has mechanisms for maintaining the
quality of the proteins synthesized. The endoplasmic reticulum has
three different sensor molecules that monitor the amounts of
improperly folded proteins that accumulate.
 Smooth endoplasmic reticulum is involved in lipid synthesis and
contains enzymes termed cytochromes P450 that catalyze
hydroxylation of a variety of endogenous and exogenous
compounds.
 These enzymes are important in biosynthesis of steroid hormones
and removal of toxic substances
Golgi apparatus
 The Golgi (named for its discoverer Camillo Golgi) apparatus is a flat,
membranous sac.
 In Golgi apparatus proteins are processed, modified and prepared
for export from the cell.
 It works in association with endoplasmic reticulum, where proteins
for certain destinations are synthesized
Figure 1.6: A Golgi apparatus and its relationship to the endoplasmic
reticulum and nucleus.
Functions of Golgi Apparatus
 Proteins which are synthesized in the endoplasmic reticulum passed
through layers of the Golgi apparatus where enzymes in Golgi
membranes catalyse transfer of carbohydrate units to proteins to
form glycoproteins or to lipids to make glycolipids, a process that is
important in determining the proteins eventual destination.
 The modified proteins are then sorted, packaged and transported to
destination inside or outside the cell. Golgi apparatus plays the role
of post office mail sorting room, the mail in this case being newly
synthesized proteins.
Mitochondrion (Power House of Cell)
 Mitochondria are called Power plant of the cell, since they generate
most of the cell’s energy in the form of ATP.
 Erythrocytes are an exception which derive their ATP from
glycolysis due to lack of mitochondria.
 Each mitochondrion is bounded by two membranes.
 The relatively porous smooth outer membrane is permeable to
most molecules.
 The inner membrane, which is impermeable to ions and a variety of
organic molecules.
 The inner membrane projects inwards into folds that are called
cristae
Figure 1.7: Structure of mitochondria.
Functions of Mitochondria
 The inter-membrane space contains several enzymes involved in
nucleotide metabolism.
 Whereas, the gel-like matrix (mitosol) consists of high concentration
of enzymes required for the metabolic pathways of oxidation of
pyruvate.
 The mitochondrial matrix is the site of most of the reactions of the
citric acid cycle and fatty acid oxidation.
 Components of electron transport system and oxidative
phosphorylation that are responsible for the synthesis of ATP are
embedded in inner membrane.
 Mitochondria also have a requisite machinery to catalyze protein
synthesis.
 Mitochondria contain their own DNA, (mtDNA), which in human
encodes 13 respiratory chain proteins, as well as small and large
ribosomal RNAs and enough tRNAs to translate all codons
 In recent years mitochondria have also been recognized as key
regulators of apoptosis.
 Mitochondria have a key role in aging; cytochrome c, a component
of the mitochondrial electron transport chain, is an initiator of
apoptosis.
Lysosomes
 Lysosomes are organelles formed from Golgi apparatus and
dispersed throughout the cytoplasm.
 The lysosomes are membrane bounded sacs containing hydrolytic
enzymes like proteases, nucleases, glycosidases, lipases,
phosphatases and sulfatases.
 All these enzymes function at acidic pH, so pH of lysosome matrix is
maintain at about 5.
Functions of Lysosomes
 Lysosomes are involved in digestion of intra- and extra-cellular
substances that must be removed.
 Substances destined to be degraded are identified and taken up by
lysosomes through endocytosis.
 During development lysosomes play an important role in the
formation of specialized tissues such as fingers and toes.
 For example, lysosomes digest the webbed tissues that join fingers
and toes in the embryo.
Peroxisomes
 Peroxisomes (organelles having ability to produce or utilize hydrogen
peroxide) are similar to lysosome in that they are membranous sacs
containing enzymes.
 The enzyme content of cellular peroxisome varies according to the
need of the tissue.
 Liver peroxisomes contain three important detoxification enzymes;
catalase, uric acid oxidase and D-amino acid oxidase.
Functions of Peroxisomes
 Peroxisomes contain enzymes that are used for detoxification rather
than for hydrolysis.
 Peroxisomes also participate in degradation of very long chain fatty
acids and synthesis of glycerolipids, plasmalogens and isoprenoids.
 In peroxisomes a number of molecules which are not metabolized
elsewhere are oxidized by enzymes by using molecular oxygen
directly and produce hydrogen peroxide (H2O2).
 Hydrogen peroxide is destroyed further by catalase and peroxidases.
Nucleus
 Nucleus is the control center of the cell; it contains the DNA
organized into chromosomes which carry genetic information.
 The nucleus is surrounded by a double membrane called nuclear
envelope.
 The outer membrane is fused with the endoplasmic reticulum at
multiple sites.
 Nuclear pores (multiprotein complexes) occur at points where the
outer and inner membranes are connected
Figure 1.8: General structure of nucleus.
Functions of Nucleus
 DNA, the repository of genetic information is located in the nucleus
as a DNA-protein complex, chromatin, which is organized in to
chromosomes.
 The nucleus contains the proteins and enzymes of replication of
DNA and for repair of DNA that has been damaged.
 The major functional role of the nucleus is that of replication,
synthesis of new DNA and transcription, synthesis of rRNA, tRNA
and mRNA.
 The processing of RNA for assembly of ribosomes, required for
protein synthesis in the cytosol, occurs in the nucleolus.
CYTOSKELETON
 The cytoplasm of most eukaryotic cells contains network of several
types of proteins filaments that interact extensively with each other
and with the component of the plasma membrane forming three
dimensional meshwork.
 Such an extensive intracellular meshwork of protein has been called
cytoskeleton.
 Cytoskeleton is not a rigid permanent framework of the cell but is a
dynamic, changing structure.
Functions of Cytoskeleton
 The cytoskeleton gives cells their characteristic shape and form,
provides attachment points for organelles, fixing their location in cells
and also makes communication between parts of the cell possible.
 It is also responsible for the separation of chromosomes during cell
division.
 The internal movement of the cell organelles as well as cell
locomotion and muscle fiber contraction could not take place
without the cytoskeleton.
 It acts as track on which cells can move organelles, chromosomes
and other things.
Structure of Cytoskeleton
The cytoskeleton is an organized network of three protein
filaments differing in width, composition and specific function:
 Microfilaments,
 microtubules and
 intermediate filaments,
 Microfilaments consist of long thin strands of protein actin, which is
also a main component of muscle.
 Actin filament form a meshwork just underlying the plasma
membrane of many cells and are referred to stress fiber or cell
cortex which is labile.
 They disappear as cell motility increases or upon malignant
transformation of cells by chemical or oncogenic viruses.
 Microtubules are long, thin tubes composed of the protein tubulin.
 They rapidly assemble into tubular structures and disassemble
depending on the needs of cells.
 Microtubules comprise the spindle fibers that separate
chromosomes prior to cell division.
 Centrioles are composed of microtubules and function as the
organizing center for the formation of spindle fibers.
 Intermediate filaments are so-called as their diameter is
intermediate between that of microfilaments and of microtubules.
 These are formed from fibrous protein which cannot be easily
disassembled as either the microtubules or the microfilaments can,
except lamin.
 Protein structure of intermediate filaments varies with different
tissue type. There are major seven classes of intermediate filaments
as indicated in.
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