Biochemistry

(Biol. 3071)

1
 Chapter 1
Introduction
• Biochemistry study about
– chemistry of living organisms.
– the chemical processes and biological substances
(molecules) at molecular level in living organisms.
– the synthesis, structure, and function of biological
macromolecules and their roles in living organisms.
– the entire spectrum of lifeforms
• scope = as vast as life itself !
• Biochemistry overlaps/related with other areas of biology and
chemistry, particularly Cell Biology, Genetics, Medicine, and
Molecular Biology.

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The origin of life
• still a big debating issue in science.
• evolution of life on earth = after Earth's formation
approximately 1 billion years later on

Life = a "condition" that distinguishes

animals and plants from inorganic
materials and dead organisms.

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Theories on Origin of life
1. Theory of Special Creation:
 life created by God, the almighty.
2. Theory of Catastrophism:
 modification of the theory of Special Creation.
 creations of life by God, each preceded by geological disturbance.
 each catastrophe completely destroyed the existing life, each new
creation consisted of life form different from that of previous ones.
3. Cosmozoic Theory (Theory of Panspermia):
 life on Earth come from other heavenly bodies in the form of highly
resistance spores of some organisms.
4. Theory of Chemical Evolution:
 life on earth is the result of a slow and gradual process of chemical
evolution

4
Other theories of life existance
• Prebiotic world theory (before life is exist) -Earth's early
atmosphere was highly reduced, rich in methane (CH4),
ammonia (NH3), water (H2O), and hydrogen (H2), and that this
atmosphere was subjected to large amounts of solar radiation
and lightning.
• In the 1950s, Stanley Miller and Harold Urey set out to
answer this question.

5
 Miller Experiment. An electric
discharge (simulating lightning)
passed through an atmosphere of
CH4, NH3, H2O, and H2 leads to the
generation of key organic
compounds such as amino acids.
This indicates that many components of
Biochemical macromolecules can be
produced in simple, prebiotic reactions.

Then the first life is exist on earth

e.g. chemoheterotrophs
e.g. cyanobacteria (blue green algae)
 Eventually complex multicellular organisms are
produced through evolution process. E.g humans
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Chapter 2
An overview of the cellular foundation of life
• Robert Hook
– the first to observe plant cells
• Schleiden and Schwann
– all living things are composed of cells
• Virchow
– cells arise only from other cells (i.e. all cells arise from
preexisting cells).

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What are cells?
• the smallest unit of life
• the structural and functional unit of all living
organisms
• On the basis of level of organization - all living cells can
be classified into two groups.
– Prokaryotes (Bacteria, Archaea, Blue green algae),
and
– Eukaryotes (Animals and plants)

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Based on the number of cells formed living organisms
can be
 Unicellular organisms (organisms made up of single
cell)
• Bacteria (Prokaryotic organism)
• Yeast (Eukaryotic organism)
• Paramecium
• Amoeba
• etc
 Multicellular organism (organism made up of two and
more than two cells)
• Animal and Plant cells

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 The main distinguishing characteristics of Prokaryotes and Eukaryotes
Characteristics of Prokaryotes Characteristics of Eukaryotes
Size 1-10µm Size 10-100µm
Their DNA is not found in the nucleus and Their DNA is found in the cell's nucleus,
usually circular which is separated from the cytoplasm by
a nuclear membrane, and the DNA is
linear and found in multiple chromosomes.
Their DNA is not associated with histones Their DNA is associated histones
They lack membrane-enclosed organelles. They have a number of membrane-
enclosed organelles, including
mitochondria, endoplasmic reticulum,
Golgi complex, lysosomes, and sometimes
chloroplasts.
Their cell walls almost always contain the Their cell walls, when present, are
complex polysaccharide peptidoglycan. chemically simple. (e.g. Cellulose in plants,
Chitin in fungi)
They usually divide by binary fission. Cell division usually involves mitosis, in
During this process, the DNA is copied, which chromosomes replicate and an
and the cell splits into two cells. identical set is distributed into each of two
nuclei. 10
Living organisms can be classified based on:
• the ability to synthesize their own food
– Autotrophs or (synthesize their own food )
– Heterotrophs (not synthesize their own food)
• energy sources
– phototrophs trap and use sunlight, and
– chemotrophs derive their energy from oxidation of a fuel
(organic nutrients)

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Chapter 3
The molecules of life
• Macromolecules of life
– macromolecules are polymers
• Polymers = molecules built by linking together a large
number of similar chemical subunits.

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Macromolecules Monomers Polymers

Carbohydrates sugars polysaccharides

Protein amino acids proteins and polypeptides

Nucleic Acids nucleotides DNA & RNA

Lipids fatty acids (membranes = non-covalent structures)

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Biological macromolecules

• Can be grouped into four major categories:

1. Proteins
2. Carbohydrates
3. Lipids, and
4. Nucleic acids (DNA & RNA)
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Key

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Amino acids, Peptides and Proteins
1. Amino acids
• are monomers or building blocks of proteins

Structure of amino acids

• For all the common amino acids, except glycine, the α-carbon is
bonded to four different groups:
– a carboxyl group
– an amino group
– an R group, and
– a hydrogen atom
• The R groups of amino acids determine their
unique biochemical functions.

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• in glycine, the R group is another hydrogen atom.
in neutral solution (pH 7), the carboxyl group exists
as –COO- and the amino group as -NH3+. Because the
resulting amino acid contains one positive and one negative
charge, it is a neutral molecule called a zwitterion.

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Types of amino acids

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Naming of amino acids
• The names of the different amino acids have been
given three-letter and one-letter abbreviations.
– the three-letter abbreviations use the first two letters in the
name plus the third letter of the name or the letter of a
characteristic sound, such as trp for tryptophan.
– the one-letter abbreviations use the first letter of the name
of the most frequent amino acid in proteins (such as an “A”
for alanine).
• If the first letter has already been assigned, the letter of a
characteristic sound is used (such as an “R” for
arginine).
• Single-letter abbreviations are usually used to denote
the amino acids in a polypeptide sequence.

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• Of the over 300 naturally occurring amino acids, 20
constitute the monomer units of proteins.
– i.e. all proteins, whether from the most ancient lines of
bacteria or from the most complex forms of life, are
constructed from the same ever-present set of 20 amino
acids.
• All the amino acids have trivial or common names, in
some cases names of amino acid derived from the
source from which they were first isolated.
– Asparagine was first found in asparagus
– Glutamate in wheat gluten;
– Tyrosine was first isolated from cheese (its name is
derived from the Greek tyros, “cheese”); and
– Glycine (Greek glykos, “sweet”) was so named
because of its sweet taste. 20
Essential amino acids
• 9 of the 20 amino acids
• they cannot synthesized in the body of neither humans
nor any other higher animals
– These are lysine, isoleucine, leucine, threonine,
valine, tryptophan, phenylalanine, methionine,
and histidine.

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Optical properties of amino acids

• In L-amino acids, the NH3+ group is found on the left, while in

D-amino acids it is on the right.

• the amino acids in proteins occur only as their L

isomers
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The L-and D-isomers of an amino acid, shown with ball-and-stick models
The two isomers. like left and right hands, are mirror images of each other and cannot
be superimposed on one another.

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Peptides

• Peptide
– short polymers of amino acids.

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peptide bond formation

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Peptide bonds are formed by condensation reaction. i.e.
Peptide bond formation results in the release of H2O.
 The side chain or R group is not part of the backbone or the peptide bond in the
primary structure of protein
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Peptide nomenclature
– Dipeptide =2aas.
– Tripeptide= 3aas
– Tetrapeptides= 4aas
– Pentapeptides= 5aas , and so forth.
– Oligopeptide = few aas may be 12-20aas
– Polypeptide= many amino acids are joined.

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Proteins
• are the most abundant biological
macromolecules in living cells
• unbranched polymers of amino acids
• all proteins in all domains of life (bacterial,
archaeal, and eukaryotic) are constructed from
the same set of 20 amino acids.

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• The peptide “backbone” of a protein consists
of the repeated sequence

-N-Cα-C-

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Proteins Are Composed of
– only one polypeptide chain = monomeric proteins
– more than one polypeptide chain = multimeric
proteins.
 multimeric proteins can be
 Homomultimeric. α2-type protein is a dimer of identical
polypeptide subunits, or a homodimer. or
 Heteromultimeric. E.g. Hemoglobin consists of four
polypeptides of two different kinds; it is an α2β2 heteromultimer.

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Multimeric proteins. E.g. Insulin
(hetromeltimeric protein)

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Insulin
The Sequence of Amino Acids in Proteins

• By convention, the amino acid sequence is

read from the N-terminal end of the
polypeptide chain through to the C-terminal
end.

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ribonuclease35 A
Levels of protein structure

i. Primary Structure:
ii. ii. Secondary structure:
e.g. α helix and β sheet conformations
iii. Tertiary Structure

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iV. Quaternary Structure
it is the overall protein structure. i.e. two or more polypeptide chains
(subunits) associate to form a functional protein.
e.g.
• Collagen = triple helix (3 subunits)
• Elastins -forms tendons & arteries
• Keratins - forms hair, quills, hoofs, nails, rich in cysteine &
cystine
• Hemoglobin = 2 alpha & 2 beta subunits (4 subunits)
• Albumins
• Globulins
• etc.
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  Protein can be Denatured (change its
structure) by temperature, pH, or salt changes
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On the basis of shape and solubility proteins can
be: fibrous, globular, or membrane.

– Fibrous proteins-
• linear structures.
• serve structural roles in cells.
• insoluble in water or in dilute salt solutions.
– Globular proteins- most enzymes
• spherical in shape. E.g. cytosolic enzymes
• soluble in aqueous solutions
– Membrane proteins
– insoluble in aqueous solutions

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Functions of Proteins
• Exhibit enormous diversity of biological functions.
For example:
• Catalysis=Enzymes
• Defense=Immunoglobulins (antibodies), bacteriocins
produced by many bacteria, kill other bacteria.
• Transport= hemoglobin, Serum albumin,
Transporter proteins help transport certain chemicals
into and out of cells, e.g. Glucose transporter
• Structure = α-Keratin, Histones, Collagen, Elastin,
Ribosome, Microtubules, Plasma membrane,

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• Motion= Some proteins play a role in the
contraction of animal muscle cells (actin and
myosin) and the movement of microbial and other
types of cells.
• Regulation=Insulin, Glucagon, lac repressor,
Somatotropin, Catabolite activator protein (CAP)
• Storage = Casein, Ferritin, Phaseolin, Ovalbumin

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• Functionally, proteins may be divided into four main categories:

– structural proteins (proteins make up many sub-cellular structures). E.g.

The flagella

– Catalyst (Enzymes)

– Regulatory proteins

– Transport proteins (found mostly in biological membranes, (e.g. permease

hemoglobin).

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Chemical Groups Other than Amino Acids in
Proteins
• proteins
– contain only amino acid residues= simple proteins.
– contain other chemical other than amino acids=
conjugated proteins
• conjugated proteins can be
– Lipoproteins - contain lipids prosthetic groups
– Glycoproteins - contain sugar groups.
– Metalloproteinase - contain a specific metal.

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Determining the primary structure of amino acids is
important for several reasons:
1. To elucidate its mechanism of action
– Example: the catalytic mechanism of an enzyme.
 Moreover, proteins with novel properties can be generated by
varying the sequence of known proteins.
2. To determine three-dimensional structures of proteins
 Primary structure is the link between genetic message and
protein's biological function.
3. In molecular pathology, a rapidly growing area of medicine
 Alterations in amino acid sequence can produce abnormal
function and disease.
– Example: sickle-cell anemia and cystic fibrosis
• result from a change in a single amino acid within a protein.
4. Evolutionary relationship
– The sequence of a protein reveals much about its evolutionary history.46
Protein Sequences and Evolution

– If two organisms are closely related,

• the sequences of their genes and proteins is similar.

– The opposite is true

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Protein Sequences and Evolution….
• Protein Sequences or amino acid sequence is used
to construct phylogenetic tree (a diagram
illustrating the evolutionary relationships among a
group of organisms).
• Related Proteins Share a Common Evolutionary Origin
proteins with related functions often show a high
degree of sequence similarity.
– Such findings suggest a common ancestry for
these proteins.
E.g.
– Oxygen-Binding Heme Proteins (Myglobin and Hemoglobin).
– Serine Proteases (Trypsin, chymotrypsin, elastase, Thrombin)
– EF-1α and EF-Tu
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Chaperons and protein folding
• chaperones

– Assistance of protein folding

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Protein misfolding and diseases
– neurological diseases,

– cystic fibrosis,

– mad cow diseases.

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• Protein Denaturation
– loss of three-dimensional structure of protein=
Denaturation
– by
• heat
• extremes of pH (strong acids and bases),
• certain organic solvents such as alcohol or acetone, and
• urea and guanidine hydrochloride,
• detergents, or
• ions of heavy metals, etc.

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 Proteins will regain their native structure and their
biological activity if returned to conditions in which the
native conformation is stable.
 This process is called renaturation.

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Methods to study proteins
Includes:
i. Purification of protein
– Salting Out (by precipitation)
– Dialysis (by using semipermeable membrane)
– Gel Electrophoresis
• Native PAGE
• SDS- PAGE
• Isoelectric focusing GE
– Chromatography
• Ion-exchange Chromatography
• Gel-filtration (Size Exclusion) Chromatography
• Affinity Chromatography
• HPLC, etc
ii. Sequencing of protein
iii. Detection of protein (Western Blotting)
iv. Determination of mass and 3D structure of protein
– The mass of a protein can be precisely determined by mass spectrometry.
– Nuclear magnetic resonance (NMR) spectroscopy, x-ray crystallography and
molecular modelling are
• the most important techniques used to determine the Three-Dimensional (3D) Protein Structure
(conformation). 53
Chapter 4 Enzymes
Enzymes
 are biological catalysts
 are molecules that can speed up (increase) the rate of
chemical reactions without being changed in the
overall process and
 are not consumed during the reaction they catalyze.

With the exception of a small group of catalytic RNA

molecules all enzymes are proteins. But not all proteins
are enzymes.
Enzymes can be:
• Simple enzymes:
– contain no chemical groups other than amino acid residues.
• i.e. they made up of only protein (polypeptide).
– E.g. Digestive enzymes such as pepsin, and trypsin are of this nature.
• Conjugate Enzymes: an enzyme formed from two
parts.
– i.e. a protein part called apoenzyme and a non-protein
part named cofactor.
Conjugate Enzymes

Enzyme function is often assisted by additional chemical

organic/inorganic molecule.
that components known as cofactors.
Cofactors can be subdivided into two groups:
 Metal ions, and
 Small organic molecules are called
Coenzymes. Often derived from vitamins,
• i.e. many vitamins are parts of coenzymes.
 coenzymes can be either tightly or loosely bound to
the enzyme.
• If tightly bound, they are called prosthetic groups.
Enzymes and Life Processes:
• Virtually all reactions in the body of living
organisms are mediated by enzymes.

i.e. Enzymes catalyze reactions involved in

all aspects of cellular life: including
– metabolism
– biosynthesis
– detoxification
– information storage
Properties of enzymes
a) globular proteins
b) specific
c) efficient (high catalytic efficiency)
d) possess active sites
e) can be extracted or separated from the cells and can
continue to function in vitro.
f) do not affect reaction equilibrium
Enzyme classification

EC 1 - Oxidoreductases
EC 2 - Transferases
EC 3 - Hydrolases
EC 4 - Lyases
EC 5 - Isomerases
EC 6 - Ligases
EC = enzyme commission
• Oxidoreductases: responsible for oxidation and reduction
processes in the cell.
• Transferases: responsible for the transfer of chemical groups
from one substrate to another.
• Hydrolases: hydrolyze carbohydrates, proteins, and lipids into
smaller molecules
– (e.g., β-galactosidase hydrolyses lactose into glucose and galactose).
• Lyases: catalyze the addition or removal of substituent groups.
• Isomerases: catalyze isomer formation.
• Ligases: catalyze the joining of two molecules, using an energy
source such as ATP.
Mechanism of enzyme action

• There are two models of enzyme action;

– lock and key model, and

– induced-fit model,
Example of Mechanism of enzyme action
lock-and key model

E + S ↔ ES ↔ E+P
• How do enzymes speed up chemical reactions?
– by lowering activation energy.

• Activation energy
• The energy required to start off chemical reaction
• The energy barrier for chemical reaction.
• The difference in free energy between the reagent(s) and the
transition state for the reaction.
The enzyme does not change
the free energies of reactants
or products and, therefore,
does not change the
equilibrium of the reaction.

67
Enzyme kinetics

• is the field of biochemistry that deals with

– the quantitative measurement of the rates of
enzyme catalyzed reactions and the systematic
study of factors that affect these rates.
General theory of enzyme action (kinetics), particularly by
Leonor Michaelis and Maud Menten in 1913.
Michaelis-Menten equation

• describes the relationship between substrate

concentration and the rate of an enzyme
reaction.
• Michaelis-Menten equation, relates the initial velocity (vi) to the
concentration of substrate [S] and the two parameters K m and
Vmax.
– The Vmax of the enzyme is the maximal velocity that
can be achieved at an infinite concentration of
substrate, and
– Km is the concentration of substrate required to reach
1⁄2Vmax of the enzyme. Hence, The Km of the enzyme for a
substrate is defined as the concentration of substrate at which vi
equals 1⁄2 Vmax
• At a hypothetical infinitely high substrate concentration, all of the
enzyme molecules contain bound substrate, and the reaction rate
is at Vmax. The approach to the finite limit of Vmax is called
saturation kinetics because velocity cannot increase any further
once the enzyme is saturated with substrate.
saturation kinetics
Lineweaver-Burk transformation
Factors Affecting Enzyme Activity

• The rate of an enzyme-catalyzed reaction is

affected by
– Temperature
– pH
– Substrate & Enzyme concentration, and
– the binding of specific regulatory molecules
(inhibitors or activators)
A. Temperature
B. pH
C. Substrate and Enzyme concentration
Substrate concentration
D. Inhibitors and Activators
• A substance that binds to an enzyme and decreases its
activity is called an inhibitor.
• Activators bind to allosteric sites and keep the
enzymes in their active configurations, thereby
increasing enzyme activity.
Enzyme inhibitors

1. Reversible inhibitor (bind with non covalent bond)

Reversible inhibitors are of three types, namely
1. Competitive inhibitor : Binds at the active site
2. Non competitive inhibitor : Binds at other site
3. Uncompetitive inhibitor : Binds to ES complex only
2. Irreversible inhibitor (bind with covalent bond.)
Competitive inhibitors
• shape and structure of inhibitor is very similar to substrate
• compete with the substrate for the same binding site
Feedback inhibition
– Very often, the end product of a biochemical
pathway acts as an inhibitor of an early reaction in
the pathway, a process called feedback inhibition.
Feedback inhibition refers to a situation in which
the end product of a pathway controls its own rate
of synthesis.
86
 Chapter 5

Carbohydrates
• are the most abundant organic molecules in nature.

• compounds with multiple hydroxyl groups (OH)

87
 Major functions of carbohydrates

1. Serve as storage form of energy, fuels,

and metabolic intermediates.

2. Structural elements
– E.g Peptidoglycan and Cellulose
– in the exoskeleton of many insects;

3. Structural framework of RNA and DNA

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90
• Carbohydrates can be covalently linked
with a variety of other molecules.
• Glycolipids

• Glycoproteins

91
Carbohydrate Nomenclature
• Carbohydrates are generally classified into
three groups:
1. Monosaccharides (and their
derivatives),
2. Oligosaccharides, and
3. Polysaccharides

92
1. Monosaccharides (e.g. Glucose, Fructose & Galactose)

• also called simple sugars

• have the formula (CH2O)n.
• are described either as aldoses (contains an aldehyde
functional group) or ketoses (contains ketone functional
group).

93
Hexoses are the most abundant sugars in nature. Nevertheless, sugars
from all these classes are important in metabolism.
94
• In a monosaccharide, a hydroxyl group is bonded to
each carbon except carbonyl group.
– If the carbonyl group is at the end of the chain, the
monosaccharide is an aldehyde;
– if the carbonyl group is at any other position, the
monosaccharide is a ketone.
• By convention, the numbering of the carbon skeleton of a
sugar begins with the carbon at or nearest the carbonyl end of
the open chain.

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• Monosaccharide stereoisomers are designated D or L
based on whether the position of the hydroxyl group
furthest from the carbonyl carbon.
• therefore, a monosaccharide is designated D if the hydroxyl
group on the highest numbered asymmetric carbon is drawn
to the right in a Fischer projection. The D-forms of
monosaccharides predominate in nature, just as L-amino
acids do.

96
– The D and L forms of a monosaccharide are mirror images of
each other.
• Stereoisomers that are mirror images of each other are called
enantiomers.

97
Cyclic (Ring) Structures and Anomeric Forms

• Fischer projections = linear form

• Haworth projections = cyclic form=in aqueous solution

98
Monosaccharides exist in solution mainly as ring structures in which the
carbonyl (aldehyde or ketone) group has reacted with a hydroxyl group in the
same molecule to form a five- or six-membered ring. The oxygen that was on
the hydroxyl group is now part of the ring, and the original carbonyl carbon,
which now contains a –OH group, has become the anomeric carbon atom. An
hydroxyl group on the anomeric carbon drawn down below the ring is in
the α-position; drawn up above the ring, it is in the β-position. This
process occurs more rapidly in the presence of cellular enzymes called
mutarotases.

99
Fischer projection formulas

100
101
Glycosides (Glycosidic bonds); N- and O-Glycosidic bonds

N- and O-glycosidic bonds

• Adenosine triphosphate (ATP)

contains a β, N-glycosidic bond.

• Lactose contains an O-glycosidic

β(1 →4) bond.

• Starch contains α-1,4 and α-1,6

O-glycosidic bonds. 102
103
2. Disaccharides and Oligosaccharides

• A disaccharide contains two monosaccharides joined by O-

glycosidic bond. Lactose, which is the sugar in milk, consists
of galactose and glucose linked through a β(1→ 4) bond
formed between the β–OH group of the anomeric carbon of
galactose and the hydroxyl group on carbon 4 of glucose.
• Oligosaccharides: derive their name from the Greek word
oligo, meaning “few,” and consist of from two to ten simple
sugar molecules. They are often found attached through N- or
O-glycosidic bonds to proteins to form glycoproteins.

104
 Disaccharides (two simple sugar molecules) are common in nature.
Maltose = glucose + glucose
Sucrose (table sugar) = glucose + fructose
Lactose (milk sugar) = galactose + glucose
 Trisaccharides (three simple sugar molecules) also occur frequently.

Enzymatic hydrolysis of sucrose-

containing flower nectar in the
digestive tract of bees catalyzed by the
enzyme invertase produces honey, a
mixture of glucose and fructose.

105
All the above reactions are condensation reactions.
• The bond holds the two monosaccharide units together is a glycosidic bond.
• If it is formed between carbon atom 1 of one α–glucose molecule and carbon
atom 4 of the other α–glucose molecule, the full name of the bond is, therefore,
α-1-4-glycosidic bond.
106
Hydrolysis of disaccharides
Note that an enzyme is needed to promote these reactions. 107
3. Polysaccharides
• may contain hundreds or even thousands of monosaccharide
units.
• may be either linear or branched polymers
• include not only those substances composed only of
glycosidically linked sugar residues but also molecules that
contain polymeric saccharide structures linked via covalent
bonds to amino acids, peptides, proteins, lipids, and other
structures.
• If a polysaccharide contains
– only one kind of monosaccharide molecule are called
homo-polysaccharides
– more than one kind of monosaccharide molecule are called
hetero-polysaccharides

108
CLASSIFICATION OF POLYSACCHARIDES

109
Storage Polysaccharides
Starch
• the most common storage polysaccharide in plants.
• exists in two forms: α-amylose (unbranched) and amylopectin (branched).
Glycogen
• the major form of storage polysaccharide in animals.
• is found mainly in the liver and skeletal muscle.
• branched
Dextran
• is mostly α(1→6)-linked polysaccharides
• is a branched polymer of D-glucose units.
• found in yeast and bacteria.
• bacterial dextrans are frequently used in research laboratories as the support
medium for column chromatography of macromolecules. I.e Dextran is
used to prepare Sephadex and Bio-gel.
110
 Structural Polysaccharides
• Cellulose
– is a linear homopolymer of D-glucose units
– is the most abundant natural polymer found in the
world.
– found in the cell walls of nearly all plants
– in cellulose the glucose units are linked by
β(1→4)-glycosidic bonds.

The cellulose molecule is an unbranched polysaccharide consisting

111
of about 10,000 β-glucose units joined by glycosidic bonds.
Chitin
• is similar to cellulose, both in its biological function and its
primary, secondary, and tertiary structure.
• is present in the cell walls of fungi and is the fundamental
material in the exoskeletons of crustaceans, insects, and
spiders.
• is the earth’s second most abundant carbohydrate polymer
(after cellulose),
• One significant difference between cellulose and chitin is
whether the chains are arranged in parallel or antiparallel.
– Natural cellulose seems to occur only in parallel arrangements.
However, chitin, can occur in either parallel or antiparallel
arrangement.

112
• Agarose= An important polysaccharide mixture isolated from
marine red algae (Rhodophyceae). The three-dimensional
structure of agarose is a double helix.
• Alginates= polysaccharides of marine brown algae
(Phaeophyceae)
• Heparin, with the highest net negative charge of the
disaccharides shown, is a natural anticoagulant substance. It
binds strongly to antithrombin III (a protein involved in
terminating the clotting process) and inhibits blood clotting.
• Hyaluronates are important components of the vitreous humor
in the eye and of synovial fluid, the lubricant fluid of joints in
the body.
• The chondroitins and keratan sulfate are found in tendons,
cartilage, and other connective tissue, whereas dermatan
sulfate, as its name implies, is a component of the
extracellular matrix of skin. 113
Self test question
• During which condition water (H2O) molecule is
removed ?
A. During formation of glycosidic bond
B. During break down of glycosidic bond
C. During formation of peptide bond
D. During break down of peptide bond
E. During cyclic (ring) structure formation of monosaccharaides
F. A and C
i.e. _______ and ____are condensation reactions where as ____
and ____ are hydrolysis reactions.
• How money H2O molecules are required to break 100
glycosidic bonds?
A. 101 B. 100 C. 99 D. 50 E. unknown
114
 Chapter 6
Lipids
 water insoluble
 because they contain a predominance of nonpolar
(hydrocarbon) groups.
 However, fatty acids, phospholipids, sphingolipids, bile salts, and,
to a lesser extent, cholesterol contain polar groups. Therefore, part
of the molecule is hydrophobic, or water-insoluble; and another
part is hydrophilic, or water-soluble. Such molecules are
described as amphipathic.
 Lipids are soluble in organic solvents
 such as methanol, acetone, chloroform, and benzene.

115
Amphipathic lipids

116
Lipids have a variety of biological roles:

– they serve as:

– fuel molecules (used for energy production)

– highly concentrated energy stores

– components of cell membranes, and

– signal molecules (e.g. hormones)

– etc 117
Functions of Lipids

118
Biologically important groups of lipids
– Fats (also known as a triglyceride or triacylglycerols),
– Phospholipids (lipids on the cell membrane),
– Carotenoids (orange and yellow plant pigments),
– Sterols (e.g cholesterol), and
– Waxes
• The most abundant lipids in living organisms are
fats, are an economical form of reserve fuel storage,
because when metabolized they yield more than twice as
much energy per gram as do carbohydrates.
• The complete oxidation of triacylglycerols to CO 2 and H2O in
the body releases approximately 9 kcal/g, more than twice the
energy yield from an equivalent amount of carbohydrate or
protein. 119
A. Stored forms of Lipids
• Fats and Oils are the principal stored forms of energy in many
organisms, are derivatives of fatty acids. i.e. Fats
(triacylglycerol) are esters of glycerol with three fatty acids.
• Generally, Fats and oils are made up of combinations of two
types of organic chemicals, fatty acids and glycerol.
– Fatty acids are carboxylic acids with hydrocarbon chains ranging from
4 to 36 carbons long (C4 to C36).
– In some fatty acids, this chain is unbranched and fully saturated
(contains no double bonds); in others the chain contains one or more
double bonds. i.e. The chain of fatty acids may be saturated
(containing no double bonds) or unsaturated (containing one or more
double bonds).
– Fatty acids with one double bond are monounsaturated fatty acids,
where as those with more than one double bond are polyunsaturated
fatty acids.
• Oleic acid is a monounsaturated fatty acid, and
• Linoleic acid is a common polyunsaturated fatty acid. 120
• Within the cell, fatty acids mainly occur as fat
droplets. In the blood, they are transported in
the hydrophobic interior of lipoproteins.
• Fats containing a high proportion of
monounsaturated or polyunsaturated fatty
acids tend to be liquid at room temperature.
– The reason is that each double bond produces a
bend in the hydrocarbon chain that prevents it
from aligning closely with an adjacent chain,
thereby limiting van der waals interactions and
permitting freer molecular motion.
121
• The most common saturated fatty acids present in
the cell are palmitic acid (C16) and stearic acid
(C18).

122
– The position of a double bond is designated by
the number of the carbon in the double bond
that is closest to the carboxyl group.
• For example, oleic acid, which contains 18 carbons and
a double bond between position 9 and 10, is designated
18:1, Δ9.
– The number 18 denotes the number of carbon atoms,
1 (one) denotes the number of double bonds.
• Another example:
– a 20-carbon fatty acid with one double bond between C-9
and C-10 (C-1 being the carboxyl carbon) and another
between C-12 and C-13 is designated 20:2(Δ 9,12).

123
Saturated fatty acids

Unsaturated fatty acids

ω Indicates that, the last carbon, and the numbers 9,3,6 shows how far it from the last double bond124
• The simplest lipids constructed from fatty acids are
the triacylglycerols, also referred to as triglycerides,
fats. Since triacylglycerols are uncharged, they are
also referred to as neutral fats.
– Triacylglycerols are composed of three fatty acids each in
ester linkage with a single glycerol.

125
The structure of triglycerides
Triacylglycerol, the main storage lipid: Glycerol is attached to fatty acids by
ester linkages (in gray). The space-filling models show the actual shapes of the
fatty acids. (c)Palmitic acid, a saturated fatty acid, is a straight chain. (d)Oleic
acid (monounsaturated) and (e)linoleic acid (polyunsaturated) are bent or
kinked wherever a carbon-to-carbon double bond appears.

126
• Vegetable oils such as corn (maize) and olive oil
are
– composed largely of triacylglycerols with
unsaturated fatty acids and thus are liquids at room
temperature.
• All fats produced by animals are saturated
(except some fish oils), while most plant fats are
unsaturated.

127
B. Structural Lipids
e.g 1. Membrane lipids
The three major kinds of membrane lipids are phospholipids,
glycolipids, and cholesterol
• Phospholipids
– formed from one glycerol, two fatty acids, and a phosphate group.
• Phospholipids are the major structural elements of biological
membranes.
• The central architectural feature of biological membranes is a
double layer of lipids, which acts as a barrier to the passage of
polar molecules and ions.
• Membrane lipids are amphipathic:
– i.e. one end of the molecule is hydrophobic, the other
hydrophilic.
128
Glycolipids
• are present in all tissues on the outer surface of
the plasma membrane. They consist of
sphingosine, a fatty acid, and an oligosaccharide
residue.
– Gangliosides are the most complex glycolipids. They
constitute a large family of membrane lipids with
receptor functions that are as yet largely unknown.
– Glycolipids are also important constituents of
nervous tissue such as brain and the outer leaflet of
the cell membrane, where they contribute to the
carbohydrates on the cell surface.

129
Cholesterol
• Cholesterol is an amphipathic lipid, is an important
component of membranes.
• It is the parent molecule from which all other steroids
in the body, including major hormones such as the
adrenocortical and sex hormones, D vitamins,
and bile acids, are synthesized.

There is no cholesterol at all in prokaryotes (with a

few exceptions). The inner mitochondrial membrane
of eukaryotes is also low in cholesterol

130
e.g 2. Sphingolipids
• are found in large quantities in the membranes of nerve cells
in the brain and in neural tissues
• have a slightly different structure from the other membrane
lipids discussed so far. In sphingolipids, sphingosine, an amino
alcohol with an unsaturated alkyl side chain, replaces glycerol
and one of the acyl residues. When sphingosine forms an
amide bond to a fatty acid, the compound is called ceramide.
This is the precursor of the sphingolipids. Sphingomyelin is
the most important sphingolipid has an additional phosphate
residue with a choline group attached to it on the sphingosine,
in addition to the fatty acid.

131
Some common types of storage and membrane lipids.
All the lipid types shown here have either glycerol or sphingosine as
the backbone (pink screen), to which are attached one or more long chain alkyl
groups (yellow) and a polar head group (blue). In triacylglycerols,
glycerophospholipids, galactolipids, and sulfolipids, the alkyl groups are fatty
acids in ester linkage. Sphingolipids contain a single fatty acid, in amide linkage
to the sphingosine backbone. The membrane lipids of archaebacteria are variable;
that shown here has two very long, branched alkyl chains, each end in ether
linkage with a glycerol moiety. In phospholipids the polar head group is joined
through a phosphodiester, whereas glycolipids have a direct glycosidic linkage
between the head-group sugar and the backbone glycerol.

132
Glycosphingolipids as determinants of blood groups
• The human blood groups (O, A, B) are determined in
part by the oligosaccharide head groups (blue) of these
glycosphingolipids.

133
Working with Lipids

• In exploring the biological role of lipids in cells and

tissues, it is essential to know which lipids are
present and in what proportions.
– Because lipids are insoluble in water, their extraction
and subsequent fractionation require the use of
organic solvents

134
 Lipid Extraction, Requires Organic Solvents

Ratio= 1:2:0.8
more polar molecules such as
proteins and sugars partition
into the methanol/water layer.

The lipids remain in the

chloroform layer Gas-Liquid
Chromatography
Resolves Mixtures
of Volatile Lipid
Derivatives
Adsorption
Chromatography
Separates Lipids of
Different Polarity

In TLC technique As the solvent rises on the

plate by capillary action, it carries lipids with on the basis of
it. The less polar lipids move farthest, as they chain length and
have less tendency to bind to the silicic acid.
The separated lipids can be detected by
degree of
spraying the plate with a dye (rhodamine) saturation by
that fluoresces when associated with lipids or HPLC
by exposing the plate to iodine fumes. Iodine
reacts reversibly with the double bonds in Determination of
fatty acids, such that lipids containing the structure of a
unsaturated fatty acids develop a yellow or fatty acid by mass
135
brown color. spectrometry
Lipids as Signals, Cofactors, and Pigments
• The two functional classes of lipids are
– Storage lipids and Structural lipids.
• Other lipids, although present in relatively small quantities,
play crucial roles as:
– potent signals- as hormones, carried in the blood from one tissue to
another, or as intracellular messengers generated in response to an
extracellular signal (hormone or growth factor).
– enzyme cofactors in electron-transfer reactions in chloroplasts and
mitochondria, or in the transfer of sugar moieties in a variety of
glycosylation (addition of sugar) reactions.
– as light-capturing pigments in vision and photosynthesis
– emulsifying agents in the digestive tract
– etc

136
Signal transduction pathways

• Signal transduction
– is the process by which a cell converts an extracellular
signal into an intracellular signal that results in some
response.

• The signal represents

– information that is detected by specific receptors and
converted to a cellular response.
 Generalized Signal Transduction Pathway

Signal → Receptor →Transducer → Effector → Response

Components of signal
transduction pathways
are similar—what
differs is the details.
Cell signaling
– requires
i) Signal (three types of signaling molecules: local
regulators, neurotransmitters, and hormones.)
ii) Cell receptor (usually on cell surface)

• Types (mechanisms) of signaling

Direct contact (e.g., gap junctions between cells)
Paracrine: Diffusion of signal molecules in
extracellular fluid; highly local
Synaptic: neurotransmitters
Endocrine: Signal (hormone) molecule travels
through circulatory system
Local regulators
include local chemical
mediators such as
growth factors,
histamine, substances
called prostaglandins,
and nitric oxide.

Some types of
cell signaling
i) Types of signal molecules

i. Local regulators = histamine, growth factors,

prostaglandins, and nitric oxide, a gaseous signaling
molecule that passes into target cells.

ii. Neurotransmitters = Several hundred types

– Some are also hormones e.g. Estrogen, progesterone

iii. Hormones= Chemically diverse

• Steroid, Polypeptide, Vitamin/amino acid derived
ii) Receptor molecules
– Receptors are large proteins or glycoproteins that
bind with signaling molecules.
A. Cell surface receptors
– Gated ion (ligand-gated) channel linked receptors
– G protein-linked receptors
– Enzyme-linked receptors
B. Intracellular receptors
• are located in the cytosol or in the nucleus.
• most of them are transcription factors, proteins that regulate the
expression of specific genes.
e.g.
• Protein that binds signal molecule in cytoplasm
• Second messengers. E.g. cAMP, Ca2+
A. Cell surface receptors

143
144
145
B. Intracellular receptors

• e.g. Second messengers (e.g. Cyclic AMP, Ca2+)

146
147
 148
Signal transduction involving a G protein and cyclic AMP
• Ca2+
– have important functions in many cell processes, including
• muscle contraction,
• blood clotting
• activation of certain cells in the immune system.
• neural signaling, including the pathways involved in learning.
• fertilization of an egg and in the initiation of development

149
The sequence of events
that takes place in cell
signaling.
i. Cell sends signal
ii. Reception
iii. Signal transduction
iv. Response

Three main types of receptors

on the cell surface are:
i. ion channel (ligand-
gated)– linked receptors,
ii. G protein–linked
receptors, and,
iii. enzyme-linked receptors.
• Role of lipids in signal transduction.
– Lipids are not just used as a passive component of
membranes, or as a source of stored energy.
• E.g. they act as ligands that activate signal transduction
pathways as well as mediators of signaling pathways,
and lipids are the substrates of lipid kinases and lipid.

151
152
153
Phospholipid products as second messengers 154
Lipids as Cofactors
• Ubiquinone (also called coenzyme Q) and
Plastoquinone are isoprenoids that function as
lipophilic electron carriers in the oxidation-
reduction reactions that drive ATP synthesis in
mitochondria and chloroplasts, respectively.

155
Lipids as Pigments
• E.g. Carotenoids (orange and yellow plant pigments)
– derived from isoprene units.
– play a role in photosynthesis

• most animals convert carotenoids to vitamin A,

– which can then be converted to the visual pigment retinal
• which is light receptor in the eye.

156
Signal transduction in microorganisms
– For example,
• bacteria release chemical signals that diffuse among
nearby bacteria.
• as the population of bacteria increases, the concentration
of the chemical signal increases.
• through a process known as quorum sensing, the bacteria
sense when a certain critical concentration of a signal
molecule is reached.
• the bacteria respond by activating a specific biological
process.
– e.g. they may form a biofilm, a community of microorganisms
attached to a solid surface.

157
• The two-component signaling mechanism in bacterial
chemotaxis. When an attractant ligand (A) binds to the
receptor domain of the membrane-bound receptor, a
protein His kinase in the cytosolic domain (component 1)
is activated and autophosphorylates on a His residue.
This phosphoryl group is then transferred to an Asp
residue on component 2 (in some cases a separate
protein; in others, another domain of the receptor
protein). After phosphorylation on Asp, component 2
moves to the base of the flagellum, where it determines
the direction of rotation of the flagellar motor.

158
159
Signaling Systems of Plants Have Some of the Same
Components Used by Microbes and Mammals

• Like animals, vascular plants have a means of communication between

tissues to coordinate and direct growth and development.

• However, some types of signaling proteins common in animal tissues are

not present in plants, or are represented by only a few genes.

• The kinds of compounds that elicit signals in plants are similar to certain
signaling molecules in mammals.
– e.g. Instead of prostaglandins, plants have jasmonate;
instead of steroid hormones, brassinosteroids.

160
Signals must be terminated
• Failure to terminate signals can lead to terrible
consequences.
– E.g., the bacterium that causes cholera is ingested when
people drink contaminated water. The cholera bacterium
releases a toxin that activates G proteins in the epithelial
cells lining the intestine. The toxin chemically changes the
G protein so that it can no longer switch itself off. As a
result, the G protein continues to stimulate adenylyl cyclase
to make cAMP. The cells lining the intestine malfunction,
allowing a large flow of chloride ions into the intestine.
Water and other ions follow, leading to the severe watery
diarrhea that characterizes cholera. The disease is treated by
replacing the lost fluid. If untreated, this G protein
malfunction can cause death.
161
 Chapter 7
Central metabolic pathways and energy transduction

• Where do cells obtain energy?

– from food molecules
• that it either manufactures by photosynthesis or obtains from the
environment

• Why do cells need energy?

– to carry out life processes
• movement, growth and development, and reproduction.
• How do cells obtain energy from food molecules?
– by metabolism process
Bioenergetics
• mechanism of energy production and utilization in
living organisms
• study about energy flow through living systems

• Examples of major bioenergetic processes

– Glycolysis, Gluconeogenesis, Citric acid cycle, Photosynthesis, etc

163
• Energy relationships
between catabolic
and anabolic
pathways. Catabolic
pathways deliver
chemical energy in
the form of ATP,
NADH, NADPH,
and FADH2. These
energy carriers are
used in anabolic
pathways to convert
small precursor
molecules into cell
macromolecules.

164
What is Adenosine triphosphate (ATP)?
• Adenosine triphosphate (ATP) is the energy currency of the
cell.

The instability of its phosphate bonds makes ATP an excellent energy donor.

• How is ATP able to transfer energy so readily?

 By phosphorylation

Example of a phosphorylation reaction

165
ATP plays a central role in cell energy metabolism by linking exergonic
and endergonic reactions. ATP transfers energy by transferring a
phosphate group.
166
ATP links exergonic and endergonic reactions

167
Phosphoryl group transfer and ATP

• ATP donates energy through the transfer of a phosphate

group.
• This is an exergonic reaction
– i.e. release around 7.3 kcal/mole)

168
ATP and ADP
ATP, the energy currency
of all living things,
consists of adenine, ribose,
and three phosphate
groups. The hydrolysis of
ATP, an exergonic
reaction, yields ADP and
inorganic phosphate. (The
black wavy lines indicate
unstable bonds. These
bonds allow the
phosphates to be
transferred to other
molecules, making them
more reactive.)

169
Biological oxidation-reduction (Redox) reactions
• Cells transfer energy through
– phosphorylation reaction. i.e. the transfer of a phosphate group from
ATP.
– transfer of electrons.
• Oxidation = loses electrons,
• Reduction= gains electrons. they occur simultaneously.

• The substance that becomes oxidized = gives up energy

• The substance that becomes reduced = receives energy

• electron transfers= equivalent to energy transfers

– are an essential part of cellular respiration, photosynthesis, and many other chemical
reactions.
• Redox reactions, for example, release the energy stored in food
molecules so that ATP can be synthesized using that energy.

170
• The transfer of phosphoryl groups is a central feature of
metabolism.
• Equally important is another kind of transfer, electron
transfer in oxidation-reduction reactions.
– i.e. the transfer of electrons in redox reactions is another way
that cells transfer energy.

171
Metabolism
• The sum total of all chemical reactions carried out by an
organism, is called metabolism.
Metabolic pathways can be:
• Linear e.g Glycolysis
• Branched
– yielding multiple useful end products from a single precursor
or
– converting several starting materials into a single product.
• Cyclic e.g. TCA cycle
– one starting component of the pathway is regenerated in a
series of reactions that converts another starting component
into a product.
172
173
Metabolism can be:

1. Catabolism = exergonic and produce ATP

2. Anabolism = endergonic and require ATP

• Photosynthesis and gluconeogenesis are also an example of anabolic
process

 catabolic pathways are convergent and anabolic pathways divergent.

Three stages of catabolism

175
176
Cellular respiration
• is the process by which cells generate ATP through a series of
biochemical redox reactions.

• a process that releases energy stored in the nutrient molecules.

• Cellular respiration may be either aerobic or anaerobic.
– Aerobic respiration requires oxygen, whereas anaerobic
respiration (e.g. fermentation), do not require oxygen.
• Both type of respiration are exergonic and they release energy in
the form of ATP, that can be captured by the cell.
– ATP is used to provide immediate energy for cells to do
work.
The diagram represents the oxidation of fuels to generate ATP, which is
called respiration

Generation of ATP from fuel

components during respiration.
• Glucose, fatty acids, and amino
acids are oxidized to acetyl CoA, a
substrate for the TCA cycle. In the
TCA cycle, they are completely
oxidized to CO2. As fuels are
oxidized, electrons (e-) are
transferred to O2 by the electron
transport chain, and the energy is
used to generate ATP.

178
Aerobic cellular respiration
– is the most efficient way to extract energy from fuels
(glucose, fatty acids, and amino acids).
E.g. Breakdown of sugar (catabolism)
– Can be accomplished by the following 4 major sub-
pathways of cellular respiration
1. Glycolysis
2. Synthesis of acetyl-CoA (intermediate step)*
3. Kreb Cycle
4. Electron transport chain
Pathway Eukaryote Prokaryote
Glycolysis Cytoplasm Cytoplasm
Intermediate step (synthesis Mitochondrial matrix Cytoplasm
of acetyl-CoA)
Krebs cycle Mitochondrial matrix Cytoplasm
Electron transport chain Mitochondrial inner Plasma membrane
179
membrane
The four stages of aerobic respiration in Eukaryotic cell

180
 181
An overview of aerobic respiration.
1. Glycolysis
• universal metabolic central pathway of glucose catabolism for
almost organisms. i.e. All Cells Use Glycolysis

• Is the process by which the oxidation of glucose to pyruvic

acid (three carbon molecules).
• The enzymes that catalyze the glycolytic reactions are in the
cytoplasm of the cell, not bound to any membrane or organelle.

End Products of Glycolysis:

2 ATP
2 NADH2
3 Pyruvic acid (Pyruvate)
NAD= Nicotinamide adenine dinucleotide
FAD= Flavin adenine dinucleotide 182
2. Formation of acetyl CoA
3. The Krebs Cycle (TCA cycle)
• Oxidation of acetyl CoA produces NADH and FADH2
4. The Electron Transport Chain
• A series of carrier molecules that are, in turn, oxidized and
reduced as electrons are passed down the chain
• Energy released can be used to produce ATP by
chemiosmosis.

183
 Glucose catabolism stage one: Glycolysis
 Occurs in the cytoplasm
 Involves a sequence of 10 reactions that convert glucose into 2
pyruvate (three carbon molecules).
• Two ATP molecules are used up early in the pathway, and four ATP
molecules are formed by substrate-level phosphorylation. This
yields a net of two ATP molecules for each molecule of glucose
catabolized.
• In addition, four electrons are harvested as NADH that can be used to form
ATP by aerobic respiration.
• The first half of glycolysis consists of five sequential reactions that convert
one molecule of glucose into two molecules of the three-carbon compound,
glyceraldehyde 3- phosphate (G3P). These reactions demand the expenditure
of ATP, so they are an energy-requiring process.
• Because each glucose molecule is split into two G3P molecules, the overall
reaction sequence yields two molecules of ATP, as well as two molecules of
NADH and two of pyruvate:
184
185
186
Glucose catabolism stage two:

The fate of pyruvate

Option one: synthesis of acetyl-CoA

187
Three possible catabolic fates of the pyruvate formed in glycolysis

188
 The TCA cycle also called Krebs or
Citric acid cycle

serves two purposes

• Bioenergetics

• Biosynthesis
– i.e. TCA intermediates as precursors for biosynthesis
e.g. it supplies precursors for several biosynthetic
pathways of amino acids, pyrimidines, purines etc.

189
Major reactions in TCA cycle

• Reaction 1: Condensation
• Reactions 2 and 3: Isomerization
• Reaction 4: The First Oxidation
• Reaction 5: The Second Oxidation
• Reaction 6: Substrate-Level Phosphorylation
• Reaction 7: The Third Oxidation
• Reactions 8 and 9: Regeneration of Oxaloacetate

190
 The Products of the Krebs Cycle

Products of one turn of the citric acid cycle. At each turn of the cycle, three NADH, one
FADH2, one GTP (or ATP), and two CO2 are released in oxidative decarboxylation
reactions. NB: from single Glucose 2 pyruvate is produced and enter in the cycle the total
191
product should be multiplied by 2.
192
193
 194
(replenishing) TCA cycle serves as biosynthesis
An overview of the electron transport chain

oxygen
e ptor is
na cc
ct ro
in al ele
Term
195
Moving Electrons through the Electron Transport Chain

197
• Complex I (NADH–ubiquinone oxidoreductase) accepts electrons
from NADH molecules that were produced during glycolysis,
the formation of acetyl CoA, and the citric acid cycle.
• Complex II (succinate–ubiquinone reductase) accepts electrons
from FADH2 molecules that were produced during the citric acid
cycle.
• Complex III (ubiquinone cytochrome C oxido-reductase) accepts
electrons from reduced ubiquinone and passes them on to
cytochrome C.
• Complex IV (cytochrome c oxidase) accepts electrons from
cytochrome C and uses these electrons to reduce molecular
oxygen, forming water in the process. The electrons
simultaneously unite with protons from the surrounding medium
to form hydrogen, and the chemical reaction between hydrogen
and oxygen produces water.

198
• pumping of protons through special channels in the
membranes of mitochondria from the inner to the
outer compartment= Chemiosmosis
• In the eukaryotic ell, the aerobic respiration occurs in
mitochondria as well as the cytoplasm. The Electron Transport
Chain (ETC) that yields the maximum ATPs is located in the
inner membrane of the mitochondria. So, the NADH made
during the glycolysis in cytoplasm have to be transferred to the
mitochondria using the shuttle system and for this, 2 ATPs are
consumed. However, in the bacterial cell, since there is no
mitochondria, the whole process of respiration occurs within
the cytoplasm so no ATP is consumed in transporting across the
organelle. Therefore, 38 ATPs are made form one glucose in
bacteria while 36 are made in an eukaryotic cell.
– i.e. because eukaryotic cells carry out glycolysis in their cytoplasm and
the Krebs cycle within their mitochondria, they must transport the two
molecules of NADH produced during glycolysis across the
mitochondrial membranes, which requires one ATP per molecule of
NADH. Thus, the net ATP production is decreased by two.
• Energy produced from complete oxidation of one glucose
using aerobic respiration
Pathway ATP Produced NADH FADH2
Produced Produced
Glycolysis 2 2 0
Intermediate step 0
(synthesis of acetyl- 0 2
CoA)
Krebs cycle 2 6 2
Total 4 10 2

Theoretical ATP produced from complete oxidation of one

glucose using aerobic respiration
By Oxidative
By Substrate- Phosphorylation
Pathway Level
Phosphorylation From NADH From FADH

Glycolysis 2 6 0
Intermediate step 0 6 0
(synthesis of acetyl-CoA) 202
Krebs cycle 2 18 4
This is true in
prokaryotic
cell (38ATP)
where as in
Eukaryotic
cell (36ATP)

203
 Theoretical
ATP yield.
The theoretical
yield of ATP
harvested from
glucose by
aerobic
respiration
totals 36
molecules.

substrate-level
phosphorylation =The
generation of ATP by the
direct transfer of
a phosphate group to
ADP from another
phosphorylated
204
molecule.
Theoretical
ATP yield.
The theoretical
yield of ATP
harvested from
glucose by
aerobic
respiration
totals 36
molecules.

205
 oxidative phosphorylation= The production of ATP using energy derived
from the transfer of electrons in the electron transport system of
mitochondria; occurs by chemiosmosis

Prokaryotic aerobic respiration summary equation:

C6H12O6 + 6O2 → 6CO2 + 6H2O + 38 ATP (net theoretical yield)
Eukaryotic aerobic respiration summary equation:
C6H12O6 + 6O2 → 6CO2 + 6H2O + 36 ATP (net theoretical yield)
206
Gluconeogenesis
• Gluconeogenesis= formation/synthesis of sugar (glucose) from
noncarbohydrate precursors

207
• Gluconeogenesis occurs in all animals, plants, fungi,
and microorganisms.
• The important precursors of glucose in animals are
three-carbon compounds such as
– lactate,
– pyruvate, and
– glycerol, as well as
– certain amino acids.
• In mammals, gluconeogenesis takes place mainly in
the liver.

208
• Gluconeogenesis and glycolysis are not identical
pathways running in opposite directions, although
they do share several steps; seven of the ten enzymatic
reactions of gluconeogenesis are the reverse of
glycolytic reactions.
– However, three reactions of glycolysis are
essentially irreversible in vivo and cannot be used
in gluconeogenesis:
 the conversion of glucose to glucose 6-phosphate by
hexokinase,
 the phosphorylation of fructose 6-phosphate to
fructose 1,6-bisphosphate by phosphofructokinase-1,
and
 the conversion of phosphoenolpyruvate to pyruvate by
pyruvate kinase. 209
210
 Opposing pathways of
glycolysis and
gluconeogenesis in rat
liver.

The glycolytic
reactions bypassed
in gluconeogenesis
are reaction 1, 3
and 10

Because the mitochondrial

membrane has no
transporter for
oxaloacetate, before
export to the cytosol the
oxaloacetate formed from
pyruvate must be reduced
to malate by
mitochondrial malate
dehydrogenase, at the
expense of NADH: 211
Pentose Phosphate Pathway(PPP)
• In most animal tissues, the major catabolic fate of
glucose 6-phosphate is glycolytic breakdown to
pyruvate, much of which is then oxidized via the
citric acid cycle, ultimately leading to the
formation of ATP.
• Glucose 6-phosphate does have other catabolic
fates, however, which lead to specialized products
needed by the cell.

212
Pentose Phosphate Pathway(PPP) ….
• also known as
– the hexose monophosphate pathway
– the hexose monophosphate shunt
– 6-phosphogluconate pathway
• Occurs in the cytoplasm of the cell like glycolysis
• No ATP is directly consumed or produced in the pathway
• Carbon one of glucose 6-phosphate is released as CO2, and
two NADPH are produced for each glucose 6-phosphate
molecule entering the oxidative part of the pathway
• The pathway provides a major portion of the body’s
NADPH, which functions as a biochemical reductant. It
also provides ribose 5-phosphate required for the
biosynthesis of nucleotides.
213
• Rapidly dividing cells, such as those of bone marrow, skin,
and intestinal mucosa, use the pentoses to make RNA, DNA,
and such coenzymes as ATP, NADH, FADH2, and coenzyme
A.
• In other tissues, the essential product of the pentose
phosphate pathway is not the pentoses but the electron donor
NADPH, needed for reductive biosynthesis
or to counter the damaging effects of oxygen radicals.
• Tissues that carry out extensive fatty acid synthesis
(liver, adipose, lactating mammary gland) or very active
synthesis of cholesterol and steroid hormones
(liver, adrenal gland, gonads) require the NADPH provided
by this pathway. Erythrocytes and the cells of
the lens and cornea are directly exposed to oxygen and
thus to the damaging free radicals generated by oxygen.
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 215
Pentose phosphate pathway
About above fig: General scheme of the pentose phosphate
pathway.
• NADPH formed in the oxidative phase is used to reduce
glutathione, GSSG and to support reductive biosynthesis.
• The other product of the oxidative phase is ribose 5-phosphate,
which serves as precursor for nucleotides, coenzymes, and
nucleic acids.
• In cells that are not using ribose 5-phosphate for biosynthesis,
the nonoxidative phase recycles six molecules of the pentose
into five molecules of the hexose glucose 6-phosphate,
allowing continued production of NADPH and converting
glucose 6-phosphate (in six cycles) to CO2

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The Glyoxylate Cycle
• Animals cannot convert acetyl-CoA derived from fatty
acids into glucose; plants and microorganisms can. i.e.
no net conversion of fatty acids to glucose occurs in
mammals. Hence, mammals cannot use acetyl-CoA as
a precursor of glucose, because the pyruvate
dehydrogenase reaction is irreversible and cells have
no other pathway to convert acetyl CoA to pyruvate.

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• Plants, yeast, and many bacteria do have a pathway (the
glyoxylate cycle) for converting acetyl-CoA to oxaloacetate,
so these organisms can use fatty acids as the starting material
for gluconeogenesis. This is especially important during the
germination of seedlings, before photosynthesis can serve as a
source of glucose. Germinating seeds can therefore convert the
carbon of stored lipids into glucose.
– i.e. The glyoxylate cycle is active in the germinating seeds of some
plants and in certain microorganisms that can live on acetate as the sole
carbon source.
• Generally, vertebrates do not have the enzymes specific to the
glyoxylate cycle (isocitrate lyase and malate synthase) and
therefore cannot bring about the net synthesis of glucose from
lipids.

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Glyoxylate cycle.
The citrate synthase,
aconitase, and
malate dehydrogenase of
the glyoxylate cycle are
isozymes of the citric
acid cycle enzymes;
isocitrate lyase and
malate synthase are
unique
to the glyoxylate cycle.
Notice that two acetyl
groups (pink) enter the
cycle and four carbons
leave as succinate (blue).

219