ALLOSTERIC ENZYME

Muhammad Wajid
Allosteric Enzyme:

 Some of the enzyme possess additional sites, known as

allosteric sites (Greek; allo-other) besides the active
sites

 Such enzyme are known as allosteric enzyme

 The allosteric sites are unique places on enzyme

molecules

 Allosteric enzymes have one or more allosteric sites

History:

 The term allosteric has been introduced by the two

Noble laureates, Monod and Jacob, to denote an
enzyme site, different from the active site

 These allosteric sites non-competitively binds molecule

other than the substrate and may influence the
enzyme activity
Properties of enzyme:

 Allosteric enzyme have one or more allosteric sites

 Allosteric sites are binding sites distinct from an

enzyme active site or substrate binding site

 Effector may be positive or negative, this effector

regulate the enzyme activity

 The enzyme activity is increased when a positive

allosteric effector binds at the allosteric site known as
activator site
Conti….
 Negative allosteric effector bind at the allosteric site
called inhibitor site and inhibit the enzyme activity

 Binding to allosteric sites alter the activity of the

enzyme, this is called cooperative binding

 Allosteric enzymes are also generally larger and

more complex than simple enzymes

 Most of them have two or more polypeptide chains or

subunits
Model of allosteric regulation:

 Two main model have been proposed to describe the

mechanistic basis of enzyme allostery

 Concerted model :

 Proposed by Monod, Wyman and Changeux .

 Sequential model:

 Proposed by Koshland, Nemethy and Allous

Concerted model:
 According to the model used (concerted model) to
study allosteric enzymes, they exists in two
conformational states:
 T (tense) and R (relaxed) state

 Allosteric activator favour ‘R’ state of the enzyme

 Allosteric inhibitors favour ‘T’ state of the enzyme
 In the absence of the allosteric modulator an
allosteric enzyme follows the hyperbolic kinetics R =
Relax (active)
Sequential model:

 Cooperativity by assuming that the enzyme/protein

molecule affinity is relative and changes as substrates
bind

 Unlike the concerted model, the sequential model

accounts for different species of the protein molecule
Sigmoid curve of allosteric enzyme:
Allosteric Enzyme Kinetics: Sigmoid Curve instead of
Hyperbola.

Figure: Sigmoid Curve Of Allosteric Enzyme (Initial

Reaction Rate Vs. Concentration Of Substrate)
Allosteric modulator:

 There are two types of allosteric modulators

 Homotropic modulator

 Heterotropic Modulator
Homotropic modulator:
 A homotropic allosteric modulator is a substrate for its
target enzyme, as well as a regulatory molecule of
the enzyme's activity

 It is typically an activator of the enzyme

 For example, O2 is a homotropic allosteric

modulator of hemoglobin
Heterotropic modulator:

 A heterotropic allosteric modulator is a regulatory

molecule that is not also the enzyme's substrate
 It may be either an activator or an inhibitor of the
enzyme
 For example, H +, CO2, and 2,3-
bisphosphoglycerate are heterotropic allosteric
modulators of hemoglobin
 2,3-BPG binds to an allosteric site on hemoglobin,
the affinity for oxygen of all subunits decreases
Enzyme Specificity:

 Enzymes are highly specific in nature, interacting with

one or few substrates and catalyzing only one type
of chemical reaction

 Substrate specificity is due to complete fitting of

active site and substrate

 Example: Oxido-reductase do not catalyze hydrolysis

reactions and hydrolase do not catalyze reaction
involving oxidation and reduction
Types of Enzyme Specificity:

 Bond Specificity

 Group Specificity

 Substrate Specificity

 Optical/Stereo Specificity

 Dual Specificity
Bond Specificity:

 In this type, enzyme acts on substrates that are similar

in structure and contain the same type of bond

 Example : Amylase which acts on α-1-4 glycosidic,

bond in starch, dextrin and glycogen, shows bond
specificity

 Lipase hydrolyze the ester bonds in different

triglycerides
Group Specificity:

 In this type of specificity, the enzyme is specific not

only to the type of bond but also to the structure
surrounding it
 Example: Pepsin is an endopeptidases enzyme, that
hydrolyzes central peptide bonds in which the amino
group belongs to aromatic amino acids e.g. phenyl
alanine, tyrosine and tryptophan
 Trypsin is an endopeptidases enzyme, that hydrolyzes
central peptide bonds in which the amino group
belongs to basic amino acids e.g. arginine, lysine and
Histidine
Conti…

 Chymotrypsin is an endopeptidases enzyme, that

hydrolyzes central peptide bonds in which the
carboxyl group belongs to aromatic amino acids
 Amino peptidase is an exopeptidases that hydrolyzes
peripheral peptide bond at amino terminal (end) of
the polypeptide chain
 Carboxy peptidase is an exopeptidases that
hydrolyzes peripheral peptide bond at carboxyl
terminal (end) of the polypeptide chain
Substrate Specificity:

 In this type of specificity, the enzymes acts only on

one substrate
 Example : Uricase ,which acts only on uric acid, shows
substrate specificity
 Maltase , which acts only on maltose, shows substrate
specificity
 Sucrase, which acts only on sucrose
 Arginase, which acts only on arginine
Types of substrate specificity:

 There are two types of substrate specificity

 Absolute specificity

 Relative specificity

 Absolute specificity is comparatively rare such as

urease which catalyses hydrolysis of urea
Optical/Stereo-specificity:

 In this type of specificity , the enzyme is not specific to

substrate but also to its optical configuration
 Example: D amino acid oxidase acts only on D amino
acids
 L amino acid oxidase acts only on L amino acids
 α- glycosidase which acts only on α- glycosidic bond,
which is present in starch, glycogen, and dextrin
 ß- glycosidase which acts only on β- glycosidic bond,
which is present in cellulose
Dual Specificity:

 The enzyme may act on two substrates by one

reaction type

 Example: Xanthine oxidase enzyme acts on xanthine

and hypoxanthine (two substrates) by oxidation (one
reaction type)