ENZYMES REGULATION
A B C D Product
• One enzyme regulates the rate of overall metabolic sequence
as per the cell demands.
• Such regulatory enzymes are capable of increasing or
decreasing their catalytic activity in response to certain
signals.
• Usually the first enzyme of the sequence is the regulatory
enzyme.
• Four major classes of enzymes:
- Allosteric or noncovalently regulated
- Covalently regulated
- Regulation by induction and repression of enzyme synthesis.
- Regulation by proteolytic cleavage

Allosteric Enzymes
• Allosteric enzymes have one or more allosteric sites
• Allosteric sites are binding sites distinct from an enzyme’s active site or
substrate-binding site
• Molecules that bind to allosteric sites are called effectors or modulators
• Binding to allosteric sites alters the activity of the enzyme. This is called
cooperative binding.
• Effectors may be positive or negative
• Effectors may be homotropic or heterotropic
• Regulatory enzymes of metabolic pathways are allosteric enzymes (eg: feedback
inhibition)

Allosteric Enzymes
 Allosteric enzymes tend to be
multi-sub unit proteins.
 The reversible binding of an
allosteric modulator (here a
positive modulator M) affects
the substrate binding site.

Allosteric regulation

Feedback allosteric inhibition
Glycine + Succinyl-CoA
δ- Aminolevulenic acid synthase
δ- Aminolevulenic acid
A
B
Haem
Homotropic effectors: Substrate itself acts as an effector
Heterotopic effectors : Metabolites other than substrate acts as modulator

covalent modifications

Covalently regulated enzymes
Phosphorylation or Dephosphorylation from specific serine, threonine or tyrosine residues of enzyme
.
Protein
OH
Ser Thr Tyr (His)
Kinase
phosphorylation
Dephosphorylation
Phosphatase
Conformational
Change
P
Glycogen phosphorylase b Glycogen phosphorylase a
Inactive Active

Enzymes regulated by induction and repression of
Enzyme Synthesis
• Induction and repression leads to alteration in the total
population of active sites.
Enzymes regulated by specific proteolytic cleavage
Pepsinogen Pepsin
Chymotripsinogen Chymotrypsin
Trypsinogen Trypsin
Procarboxypeptidases Carboxypeptidases
Proelastase Elastase
Cascade regulatory mechanism
Blood Coagulation