ENZYME REGULATION
Regulation of enzyme quality : Regulation of enzyme quantity:
fine regulation Coarse regulation
Short term Long term
Allosteric regulation Induction / Repression
Covalent modification Control of enzyme degradation
Compartmentalisation
Feed back regulation
Regulation of enzyme quality
• Allosteric regulation
• Covalent modification
• Compartmentalisation
• Feed back regulation
ALLOSTERIC REGULATION
• Allosteric enzyme has :
• Catalytic site where the substrate binds
• Allosteric site where the modifier molecule binds
• Allosteric enzymes are those whose activity at the active site may be
modulated by the presence of effectors at an allosteric site
TYPES
• Allosteric activators
• Allosteric inhibitors
• Allosteric activators • Allosteric inhibitors
• Binding of regulatory molecule • Binding of regulatory molecule
enhance the enzyme activity inhibit enzyme activity
• Regulatory molecule – positive • Regulatory molecule – negative
modifier modifier
• Partially reversible if excess
substrate is added
Characteristics
• Effect of allosteric modifier is maximum at or near substrate
concentration equivalent to Km
• When substrate is fixed at the catalytic site, the inhibitor binding at
allosteric site is reduced
• Most allosteric enzymes possess quaternary structure
• Does not follow Michaelis – Menten hyperbolic kinetics, gives sigmoid
kinetics
Saturation curve
EXAMPLES
COVALENT MODIFICATION
• The activity of enzymes may be increased or decreased by
covalent modification.
• It means, either addition of a group to the enzyme protein by a
covalent bond; or removal of a group by cleaving a covalent bond.
• Zymogen activation by partial proteolysis is an example of covalent
activation.
• Commonest type of covalent modification is the reversible protein
phosphorylation. The phosphate group may be attached to serine,
threonine or tyrosine residues.
• Irreversible- partial proteolysis / zymogen activation
• Reversible- addition / removal of a particular group
Partial proteolysis
• Certain enzymes are synthesized & secreted as inactive precursors –
proenzymes or zymogens
• Selective proteolysis make them catalytically active
• Eg: Gastro-intestinal enzymes, lysosomal proteolytic enzymes,
coagulation factors
Reversible
• Addition / removal of a group by making / breaking covalent bond
can either increase / decrease the catalytic activity
• Common methods include,
• Phosphorylation / dephosphorylation
• Methylation
• Adynylation
• ADP ribosylation
Phosphorylation/ dephosphorylation
• Most common type
• Phosphorylation catalysed by protein kinases
• Dephosphorylation catalysed by protein phosphatases
• They act on more than one substrate
ENZYMES ACTIVE IN ENZYMES ACTIVE IN
PHOSPHORYLATED STATE DEPHOSPHORYLATED STATE
• Glycogen phosphorylase active • Key enzymes of Glycolysis
in the phosphorylated form
• Acetyl CoA carboxylase
• HMG CoA reductase kinase
• Pyruvate dehydrogenase
• Key enzymes of
Gluconeogenesis
• HMG CoA reductase
FEEDBACK REGULATION
• End product of pathway “feed back” and control their own synthesis,
which is different from feed back inhibition
• Usually act at the level of gene expression
• Eg: control of hepatic cholesterol synthesis by dietary cholesterol
COMPARTMENTALISATION
• Anabolic and catabolic pathways occur in different cellular organelles
or compartments
• Eg: Fatty acid synthesis – cytoplasm
• Fatty acid oxidation – mitochondria
• Protein & carbohydrate degrading enzymes reside inside lysosomes
• Sometimes different reactions of the same pathway occur in different
compartments
• Eg: Heme synthesis, Urea cycle, Gluconeogenesis
• Ensures metabolic efficiency, simplifies regulation
REGULATION OF ENZYME QUANTITY
• Induction/Repression
• Control of enzyme degradation
INDUCTION/ REPRESSION
• By means of inducer / repressor
• Acts at the genetic level
• Effect occur after a lag period ( hours or days)
• Number of enzyme molecules increased / decreased in the presence
of inducer / repressor
• Induction is effected through the process of derepression.
The inducer will relieve the repression on the operator site
and will remove the block on the biosynthesis of the enzyme
molecules.
• Classical example is the induction of lactose-utilizing enzymes in the
bacteria when the media contains lactose in the absence of glucose.
REPRESSION
• Repressor acts at the gene level
• The effect is noticeable only after a lag period of hours or days
• The number of enzyme molecules is reduced in the presence of
repressor molecule
Examples
CONTROL OF ENZYME DEGRADATION
• Mammalian proteins are degraded both by
❑ Ubiquitin dependent pathways
❑ ATP independent pathways
• Influenced by intracellular ligands, physiological, hormonal & dietary
factors
• Eg: Tryptophan decrease degradation of tryptophan oxygenase
