Allosteric Enzymes and their regulation

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