1) Allosteric enzymes have additional sites called allosteric sites that are distinct from the active site. Binding of an effector molecule to these sites can induce a conformational change in the active site, increasing or decreasing the enzyme's activity. 2) There are two main models that describe allosteric regulation - the concerted model where binding causes simultaneous changes in all subunits, and the sequential model where changes occur sequentially. 3) Allosteric enzymes exhibit sigmoidal kinetics curves rather than traditional hyperbolic curves due to their cooperative binding behavior. Positive allosteric effectors increase enzyme activity while negative effectors decrease it.

1. Allosteric
enzymes
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2.  INTRODUCTION.
PROPERTIES OF ALLOSTERIC ENZYME.
KINETIC PROPERTY OF ALLOSTERIC ENZYME.
CONFORMATIONAL CHANGES.
MODEL OF ALLOSTERIC REGULATION.
SIGMOID CURVE OF ALLOSTERIC ENZYME.
ALLOSTERIC EFFECTOR.
POSITIVE EFFECTOR.
NEGETIVE EFFECTOR.
TYPES OF ALLOSTERIC REGULATION.
HOMOTROPIC.
HETEROTROPIC.
ALLOSTERIC INHIBITION.
APPLICATION.
CONCLUSION.
REFERENCES.
CONTENT
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3. 3
Enzymes:
Enzymes may be defined as biocatalysts synthesized by living cells. They are protein in nature,
colloidal and thermolabile in character and specific in their action. They are known as catalyst
of life. They accelerate the rate of reaction.
Berzelius in 1836 coined the term catalysis.
In 1878, Kuhne used the word enzyme to indicate to indicate the catalysis taking place in the
biological systems.
Allosteric Enzyme:
Some of the enzymes possess additional sites, known as allosteric sites (Greeek; allo-other)
besides the active site. Such enzymes are known as allosteric enzyme. The allosteric sites are
unique places on the enzyme molecules; allosteric enzymes have one or more allosteric site.
INTRODUCTION

4. 4
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 ,which non competitively bands
molecule other than the substrate and may influence the enzyme activity.

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•Allosteric enzyme have one or more allosteric sites
•Allosteric sites are binding sites distinct from an enzyme active site or substrate binding site
•Molecule that bind to allosteric sites are called effector or modulator
•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. On the other hand, 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 display sigmoidal plot of V₀ vs [S].
PROPERTIES OF ALLOSTERIC ENZYME

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According to the term of conformational changes:-
•Most of the allosteric enzyme are oligomeric in nature, the subunit may be identical or
different.the non covalent reversible binding of the effector molecule at the alosteric sites
bring about a confirmational changes in the active site of the enzyme,leding to the inhibition or
activation of the catalytic activity.
KINETIC PROPERTY OF ALLOSTERIC ENZYME

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Two main model have been proposed to describe the mechnastic basis of enzyme allostery:
Concerted model :Given by MONOD,WYMAN AND CHANGEUX .
Sequential model: Given by KOSHLAND, NEMETHY AND ALLOUS
MODEL OF ALLOSTERIC REGULATION

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Concerted model:
Figure: Concerted model of allosteric Regulation

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Sequential model:
Figure: Sequential Model of Allosteric Regulation

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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)

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Why Sigmoid Curve:

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ALLOSTERIC EFFECTOR
 Positive allosteric effector.
 Negative allosteric effector.
It has been suggested that allosteric effectors are:
Fig: Allosteric modulation of an enzyme

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TYPES OF ALLOSTERIC REGULATION
Homotropic
Heterotropic
Homotropic:
•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:
•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.

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• For example, when 2,3-BPG binds to an allosteric
site on hemoglobin, the affinity for oxygen of all
subunits decreases. This is when a regulator is
absent from the binding site.
• The interaction of 2,3-bisphosphoglycerate (BPG)
with hemoglobin molecules further refines the
function of hemoglobin, and provides an example
of heterotropic allosteric modulation.

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Fig. Effect of BPG on oxygen binding to hemoglobin

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ALLOSTERIC INHIBITION
Heterotropic Inhibition: The effector may be different from the substrate, in this case
effector is saidto be heterotropic effector. For example the feedback mechanism.
•Feed back inhibition
Fig: Feedback inhibition of a metabolic pathway.

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Fig: Example of Feedback Inhibition

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APPLICATION
•Recently, the combined use of physical techniques (for example, x-ray crystallography and
solution small angle x-ray scattering or SAXS) and genetic techniques (site-directed
mutagenesis or SDM) has enabled researchers to investigate more deeply the molecular
basis of allostery.
• The Escherichia coli enzyme aspartate carbamoyltransferase (ATCase) has established
itself as one of the model system's for allosteric regulation. However, it is irrefutable that the
canonical allosteric system that has shaped our current understanding of allostery is
tetrameric vertebrate Hemoglobin.
•Long-range allostery is especially important in cell signaling.
•Pharmacology