This document discusses allosteric enzymes, which have an additional regulatory site besides the active site. Allosteric enzymes are often oligomeric and have quaternary structure. The binding of effectors like allosteric inhibitors or activators at the regulatory site causes a conformational change that increases or decreases the enzyme's activity. Key metabolic enzymes are often regulated allosterically, allowing feedback inhibition that efficiently controls biochemical pathways. Examples of allosterically regulated enzymes include aspartate transcarbamylase and HMG-CoA reductase.

1. ENZYME
Regulation

2. Allosteric Enzymes

3. Allosteric Enzymes
Allosteric means the other side
So allosteric enzymes have an
additional site, besides the active
site.
Allosteric and substrate binding
sites may or may not be physically
adjacent
Both sites may be away from each
other on separate protein chains

4. Action of Allosteric Enzyme
C A

5. Properties of Allosteric enzymes
They are oligomeric proteins, that is they
have more than one polypeptide chain.
Most allosteric enzymes have quaternary
structure. They are made up of subunits
 eg: Aspartate Transcarbamylase
---6subunits
Pyruvate Kinase --- 4 subunits

6. Vo vs [S] plots give sigmoidal curve
for at least one substrate

7. The inhibitor is not a substrate
analogue
Km is usually increased,Vmax reduced.
Binding of this allosteric inhibitor
or this activator does not effect
Vmax, but does alter Km
Allosteric enzyme do not follow M-
M kinetics

8. Certain substances called modulators
bind to the other site and bring about
conformational change in the
molecule
The binding of the regulatory
molecule may either enhance the
activity of the enzyme (allosteric
activation) or inhibit the activity of the
enzyme (allosteric inhibition)
Enzyme Modulators

9. They are termed as +ve modulators if
they increase or –ve modulator if they
decrease the activity of enzyme
The effect of allosteric modifier is
maximum at or near substrate
concentration equivalent to km
When inhibitor binds to the allosteric
site, the configuration of catalytic site
is modified so that substrate cannot
bind properly

10. Allosteric Modulation

11. Key Enzymes
The body uses allosteric enzymes for
regulating metabolic pathways. Such
regulatory enzymes in a particular
pathway is called the Key Enzyme or
rate limiting enzyme.
The flow of the whole metabolic
pathway is constrained.

12. Allosteric T to R transition
Concerted model Sequential model
ET-I ET ER ER-S
I
I S

13. Regulation of Enzyme Activity
(biochemical regulation)
• 1st
committed step of a biosynthetic pathway
or enzymes at pathway branch points often
regulated by feedback inhibition.
• Efficient use of biosynthetic precursors and
energy
A B C
1 3”
3’
2
E F G
4’ 5’
H I J
4” 5”
X X DX

14. The allosteric inhibitor is most
effective when the substrate
concentration is low
This is metabolically very significant
When more substrate molecules are
available, there is less necessity for
stringent regulation.

15. Eg: A) Succinyl CoA + Glycine
↕ ALA Synthase
delta amino Levulinic acid
 First step in Heme Biosynthesis, end product
heme will allosterically inhibit ALA Synthase
 B) Aspartate Transcarbamylase
Carbamyl Phosphate + Aspartate
↕ Aspartate Transcarbamylase
Carbamyl Aspartate + Pi
 First step in CTP synthesis,CTP inhibits
Aspartate Transcarbamylase .

16. Examples of Allosteric Enzyme
S.No ENZYME Allosteric Inhibitor Allosteric activator
1 HMG Co A –reductase Cholesterol
2 Phosphofructokinase ATP,Citrate AMP,F2,6,P
3 Pyruvate Carboxylase ADP Acetyl Co A
4 Acetyl CoA Carboxylase AcylCoA Cirate
5 Citrate Synthase ATP
6 Carbamyl Phosphate
Synthetase- I N-Acetyl Glut
7 Carbamyl Phosphate
Synthetase-II UTP
8 Aspartate Transcarbamylase CTP ATP