The G provides no information about

the rate of a reaction.

An endergonic reaction is one that
absorbs free energy from its
An exergonic reaction
surroundings. proceeds with a net
Endergonic reactions store energy, release of free energy
G is positive, and and G is negative.
reaction are non-spontaneous.
 Enzymes Alter Only the Reaction Rate and Not
the Reaction Equilibrium
A negative G indicates that a reaction can occur spontaneously, but it
does not signify whether it will proceed at a perceptible rate. The
rate of a reaction depends on the free energy of activation (G),
which is largely unrelated to the G of the reaction.

Enzymes accelerate the attainment of equilibrium but do not shift

their positions. The equilibrium position is a function only of the free-
energy difference between reactants and products.
 Activation Energy vs Free Energy

There is an energy barrier that separates the energy levels of the

reactants and products. Energy must be added to the reactants to
overcome the energy barrier, which is recovered when products are
formed. The energy barrier is known as Ea, the activation energy.

The activation energy is distinct from the G, or free energy difference

between the reactants and products.
 The effect of enzymes on reaction rate
Enzyme 1 Enzyme 2 Enzyme 3
A B C D
Reaction 1 Reaction 2 Reaction 3
Starting Product
molecule
The activation energy, EA
Is the initial amount of energy needed to start a chemical reaction
Is often supplied in the form of heat from the surroundings in a system
An enzyme catalyzes reactions by lowering the EA barrier
 The catalytic cycle of an enzyme
Enzymes usually specific to one substrate.
Each chemical reaction in a cell requires its own enzyme.
1 Substrates enter active site; enzyme
changes shape so its active site 2 Substrates held in
embraces the substrates (induced fit). active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.

Substrates Enzyme-substrate 3 Active site (and R groups of

complex its amino acids) can lower EA
and speed up a reaction by
Orienting substrates correctly
6 Active site
Straining substrate bonds
Is available for
two new substrate
Mole.
Enzyme

5 Products are
Released. 4 Substrates are
Converted into
Figure 8.17 Products Products.
 Cofactors
Many enzymes require an additional small molecule, known
as a cofactor to aid with catalytic activity.
A cofactor is a non-protein molecule that carries out
chemical reactions that cannot be performed by the
standard 20 amino acids.
Co-factors play a role in catalysis, by converting inactive
apoenzyme (protein only) to an active holoenzyme
An apoenzyme together with its cofactor(s) is called a
holoenzyme
Cofactors can be either inorganic molecules (metals) or small
organic molecules (coenzymes).
Most cofactors are not covalently bound but instead are
tightly bound. However, organic prosthetic groups such as an
iron ion or a vitamin can be covalently bound
 Cofactors

Cosubstrate is changed during the reaction, dissociates from the

active site and the structure is regenerated in a subsequent
reaction by another enzyme so that it is recycled repeatedly within
the cell.
A prosthetic group remains bound to the enzyme during the
reaction ( can be covalently bound or tightly bound by many weak
interactions
 Cofactors
Mammals need a source of coenzymes in order to survive
The ones they cannot synthesise are supplied by nutrients
These essential compounds are called vitamins (vital amine)
The source of vitamins are usually plants and microorganisms
Two classes of Vitamins :
Water soluble (B vitamins) required daily in small amounts
because they are readily excreted in the urine and cellular
stores of their coenzymes are not stable
Fat soluble (lipid vitamins; A,D,E and K) are stored in animals
and excessive intake can be toxic

Coenzymes: Nucleo(s)tide
ATP: Transfer of
phosphoryl group produces
ADP ; and the transfer of
the nucleotidyl group (AMP)
generates Pryophosphate

S-adenosylmethionine: acts as a donor of the

methyl groups in biosynthetic reactions.
 ATP
Di and triphosphates form complexes with Magnesium
in both aqueous solution and the active site
These cations coordinate with oxygen atoms of the
phosphate groups
 ATP
Factors contributing to the large amount of energy released during
hydrolysis of phosphoanhydride bonds
Electrostatic repulsion among the negatively charged oxygen
of phosphoanhydride groups
The products of its hydrolysis (ADP, AMP, Pi and PPi are
better solvated than ATP
Resonance stabilisation: the products of its hydrolysis are
more stable than ATP
When a molecule has resonance structures it means there
are several possible ways in which the electrons can be
distributed in the molecule.
 Resonance stabilisation
is a way of describing delocalized electrons within certain molecules or polyatomic ions
where the bonding cannot be expressed by one single Lewis formula

The electrons on the terminal oxygen atoms are more

delocalised
 ATP
All the phosphoanyhdrides of nucleoside triphosphates have
nearly equal standard Gibbs Free energy of hydrolysis
ATP is usually the phosphoryl donor when nucleoside mono- and
diphosphates are phosphorylated
The concentrations of the nucleotides differ; i.e. intracellular
levels of ATP are higher that dTTP
ATP is involved in many reactions; because of its relative
abundance, ATP is usually the phosphoryl group donor in cells
ATP Hydrolysis powers three types of cellular work
Mechanical work,
beating of cilia, P i
P
contraction of muscle
cells, and movement Motor protein Protein moved
of chromosomes (a) Mechanical work: ATP phosphorylates motor proteins

Transport work, Membrane

protein ADP
pumping substances ATP +
P i
across membranes P P i
against the direction Solute Solutetransported
of spontaneous (b) Transport work: ATP phosphorylates transport proteins
movement
P
NH2
Chemical work, driving Glu + NH3 + P i
Glu
endergonic reactions such
Reactants: Glutamic acid Product (glutamine)
as the synthesis of and ammonia made
polymers from monomers (c) Chemical work: ATP phosphorylates key reactants
Nicotinamide Coenzymes: NAD+ and NADP +

Vitamin B3
-Humans can synthesize nicotinamide cofactors from tryptophan
-NAD and NADP act as soluble electron carriers between
proteins
-Niconitic acid has been used to reduce plasma cholesterol
 Nicotinamide Coenzymes: NAD+ and NADP +

These coenzymes play a role in oxidation-reduction reactions

The oxidised forms are electron deficient ; and the reduced form carry extra pair of
electrons in the form of a covalently bound hydride ion.
The sign shows that N atom carries a positive charge, not that the entire
molecule is positively charged (it is negatively charged due to phosphates
 Nicotinamide Coenzymes: NAD+ and NADP +

NAD+ and NADP + act as cosubtrates for dehydrogenases

They are reducing agents
 flavin Coenzymes: FAD and FMN

VitB2- Flavins are RiboFlavin: Ribitol linked

yellow in color and are light sensitive to isoalloxazine ring

Flavin mononucleotide (FMN):

Riboflavin + Phosphate (Black)

Flavin adenine dinucleotide:

FMN + Adenine monophosphate (Black and blue)
Flavin Coenzymes: FAD and FMN
The oxidation occurs in two
steps:
A single electron is removed
with a loss of a proton to
produce a stable free-radical
intermediate
The semiquinone is oxidised
by removing a proton and
an electon to form a full
oxidized FMN or FAD

Their oxidation is often coupled to

reduction of metalloprotein containing
Fe3+ (Fe-S cluster)
Oxidoreductase require FAD and FMN
as prosthetic groups
Thiamine Diphosphate

Oxidative decarboxylation reactions

Deficiency in thiamine causes beriberi

TDP is a prosthetic group for

decarboxylases and
transketolases
 Pyridoxal Phosphate

Vitamin B6

PLP is a prosthetic group for

enzymes that catalyse a variation
of reactions that involve amino
acids such as isomerisation,
decarboxylations or side-chain
replacements
 Biotin

Vit H

Biotin is a prosthetic group for enzymes that catalyse carboxyl

group transfer reactions and ATP-dependent carboxylation reactions
The carboxylate group is covalently bound via amide linkage to
lysine
 Lipoamide

Lipoamide is a protein bound form of lipoic acid, it is covalently

bound to lysine residue of the protein
It carries acyl groups between active sites in multienzyme
complexes (e.g. pyruvate dehydrogenase complex)
Coenzyme A and Acyl carrier protein

3 major components: 2-mercaptoethylamine

with a free SH group, Vitamin B5 and ADP
moiety
Coenzyme A is involved in acyl-group transfer
reactions
The reactive centre is -SH group
Acyl groups covalently attach to SH groups to
form thioester