Enzyme Induction and enzyme inhibition

Enzyme Induction and
enzyme inhibition


At the end of this lecture,
student will be able to

• Explain enzyme Induction

• Explain enzyme inhibition


• Enzyme inhibitor is defined as substance which binds with
the enzyme and brings about a decrease in catalyrtc activity of that enzyme

• The inhibitor may be organic or inorganic in nature

• There are three broad categories of enzyme inhibition

1. Reversible inhibition

2. Irreversible inhibition

3. Allosteric inhibition

1. Reversible

• The inhibiior binds non-covalently with enzyme and the
enzyme inhibition can be reversed if the inhibitor is removed

• Further sub-divided into

l. Competitive inhibition

ll. Non-competitive inhibition

l. Competitive
The inhibitor (l) which closely resembles the real substrate
(S) is regarded as a substrate analogue

• The inhibitor competes with substrate and binds at the
active site of the enzyme but does not undergo any catalysis.  As long as the competitive inhibitor

As long as the competitive inhibitor holds the active
site, the enzyme
is not available for the substrate to bind

• The relative concentration of the substrate and inhibitor
and their respective affinity with the enzyme determines the degree of
competitive inhibition

• The inhibition could be overcome by a high substrate

• ln competitive inhibition, the KM-value increases whereas
Vmax remains unchanged

• The enzyme succinate dehydrogenase (SDH) is a classical
example of competitive inhibition with succinic acid as its substrate.

• Methanol is toxic to the body when it is converted to
formaldehyde by the enzyme alcohol dehydrogenase (ADH). Ethanol can compete
with methanol for ADH. Thus, ethanol can be used in the treatment of methanol

Some examples of
competitive inhibitors are

ll. Non-competitive

• The inhibitor binds at a site other than the active site
on the enzyme surface

• This binding impairs the enzyme function

• The inhibitor has no structural resemblance with the
substrate, However exists a strong affinity for the inhibitor to bind at the
second site

• Inhibitor does not interfere with the enzyme-substrate
binding, but the catalysis is prevented, due to distortion in the   enzyme conformation

• The inhibitor generally binds with the enzyme as well as
the ES complex

• For non-competitive inhibition, the KM value is unchanged
while Vmax is lowered

• E.g.  Heavy metal
ions (Ag+, Pb2+, Hg2+ etc) can non-competitively inhibit the enzymes by binding
with cysteinyl sulfhydryl groups

• The general reaction for Hg2+ is shown below

2. lrreversible

• The inhibitors bind covalently with the enzymes and
inactivate them, which is irreversible

• These inhibitors are usually toxic poisonous substances

• Iodoacetate  is  an 
irreversible  inhibitor  of 
the  enzymes  like 
papain  and glyceraldehyde
3-phosphate dehydrogenase, here Iodoacetate combines with sulfhydryl (-SH)
groups at the active site of these enzymes and makes them inactive

• Di-isopropyl fluorophosphate (DFP) is a nerve gas
developed by the Germans during Second World War. DFP irreversibly binds with
enzymes containing serine at the active site, e.g.  Serine proteases, acetylcholine esterase.

• Many organophosphorus insecticides like melathion are
toxic to animals (including man) as they block the activity of acetylcholine
esterase (essential for nerve conduction), resulting in paralysis of vital body

• Disulfiram used in the treatment of alcoholism,
irreversibly inhibits the enzyme aldehyde dehydrogenase

• Penicillin antibiotics act as irreversible inhibitors of
serine – containing enzymes and block the bacterial cell wall synthesis

• lrreversible inhibitors are frequently used to identify
amino acid residues at the active site of the enzymes and also to understand
the mechanism of enzyme action

3. Allosteric

• The details of this type of inhibition are given under
allosteric regulation as a part of the regulation of enzyme activity in the
living system

• Some enzymes are called allosteric enzymes, they exist in
alternate higher order structures

• Binding of ligand can either enhance the activity of the
enzyme or inhibit it

• The allosteric sites are unique places on the enzyme

• Allosteric enzymes possess a site distinct and physically
separate from the substrate binding site and is called as allosteric site.

• Allosteric modulators bind to allosteric site by
reversible, non-covalent interactions.

Allosteric effectors

• Certain substances referred to as allosteric modulators
(effectors or modifiers) bind at the allosteric site and regulate the enzyme
activity. The enzyme activity is increased when a positive (+) allosteric
effector binds at the allosteric site known as activator site.

• On the other hand, a negative (-) allosteric effector
binds at the allosteric site called inhibitor site and inhibits the enzyme

The allosteric site at which the positive modulator binds is
referred to as an activator site, the negative modulator binds at an inhibitory

Classes of
allosteric enzymes

• Enzymes that are regulated by allosteric mechanism are
referred to as allosteric enzymes.

• They are divided into two classes based on the influence
of allosteric effector on Km, and Vmax:

K-class of allosteric enzymes

V-class of allosteric enzymes

Enzyme Induction

Enzyme specificity

• Enzymes are highly specific in their action when compared
with the chemical catalysts

• 3 types of enzyme specificity are well-recognised

1. Stereospecificity

2. Reaction specificity

3. Substrate specificity

1. Stereospecificity
or optical specificity:

• Stereoisomers are the comoounds which have the same
molecular formula, but differ in their structural configuration

• The enzymes act only on one isomer and therefore, exhibit

e.g. L-amino acid oxidase and D-amino acid oxidase act on L-
and D-amino acids respectively

Hexokinase acts on D-hexoses; Glucokinase on D-glucose

• The class of enzymes belonging to isomerases do not
exhihit stereospecificity since they are specializedin the interconversion of

2. Reaction

• The same substrate can undergo different types of
reactions, each catalysed by a separate enzyme and this is referred to as
reaction specificity

e.g. Amino acid undergo transamination, oxidative
deamination, decarboxylation, racemization etc.

3. Substrate

• The substrate specificity varies from enzyme to enzyme

• lt may be either absolute, relative or broad

Absolute substrate

• Certain enzymes act only on one substrate e.g. glucokinase
acts on glucose to give glucose-6-phosphate, urease cleaves urea to ammonia and
carbon dioxide

Relative substrate

• Some enzymes act on structurally related substances, may
be dependent on the specific group or a bond present

• Gorup specificity

• e.g. Trypsin 
hydrolyses peptide linkage involving arginine or lysine Chymotrypsin
cleaves peptide bonds attached to aromatic amino acids (phenylalanine, tyrosine
and tryptophan)

Bond specificity:
Examples of bond specificity specificity glycosidases acting on glycosidic
bonds of carbohydrates, lipases cleaving ester bonds of lipids etc

Broad specificity:

• Some enzymes act on closely related substrates which is
commonly known as broad substrate specificity

• e.g. hexokinase acts on glucose, fructose/mannose and
glucosamine and not on galactose

of enzyme action

• Catalysis is the prime function of enzymes, for any
chemical reaction to occur, the reactants have to be in an activated state

• The energy required by the reactants to undergo the
reaction is known as activation energy

• The reactants when heated attain the activation energy
& enzyme in the biological system reduces the activation energy and this
causes the reaction to proceed at a lower temperature

• Enzymes do not alter the equilibrium constants, they only
enhance the velocity of the reaction

• The enzymes reduce the activation energy of the reactants
in biological systems to undergo at body temperature (below 40oC)

• Enzyme-substrate complex formation:

• Substrate (S) must combine with the enzyme (E) at the
active site to form enzyme-substrate complex (ES) which ultimately results in
the product formation (P)

E + S↔ES + E + P

• A few theories have been put forth to explain mechanism of
enzyme- substrate complex formation

Lock and key model or
Fischer’s template theory

• By German biochemist Emil Fischer

• According to this model, the structure or conformation of
the enzyme is rigid

• The substrate fits to the binding site just as a key fits
into the proper lock

• Thus the active site of an enzyme is a rigid and
pre-shaped template where only a specific substrate can bind

• This model does not give any scope for the flexible nature
of enzymes, hence the model totally fails to explain many facts of enzymatic

Induced fit theory or
Koshland’s model

• By Koshland, in 1958, proposed a more acceptable model for
ES complex formation

• According to this model, the active site is not rigid and

• The interaction of the substrate with the enzyme induces a
fit or a conformation change in the enzyme, resulting in the formation of a
strong substrate binding site

• Further, due to induced fit, the appropriate amino acids
of the enzyme are repositioned to form the actives and bring about the

Substrate strain

• In this model, the substrate is strained due conformation
change in the enzyme to the induced

• When a substrate binds to the preformed active induces a
strain to the substrate site, the enzyme

• The strained substrate leads to the formation of product

• Therefore, combination of the induced fit model with the
substrates train is considered to be operative in the enzymatic action


• Enzyme inhibitor is defined as substance which binds with
the enzyme and brings about a decrease in catalyrtc activity of that enzyme

• Enzyme inhibition are of their type’s Reversible
inhibition, Irreversible inhibition & Allosteric inhibition

• Enzymes are highly specific in their action when compared
with the chemical catalysts

• 3 types of enzyme specificity are well-recognised,
Stereospecificity, Reaction specificity & Substrate specificity

• Lock and key model, Induced fit theory & Substrate
strain theory have been put forth to explain mechanism of enzyme-substrate
complex formation

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