Enzyme Regulation Mechanisms

Expansion

Fast: allosteric regulation (milliseconds)

• Effectors bind a site distinct from the active site, altering conformation
• Feedback inhibition by the end product, as ATP and citrate inhibit phosphofructokinase
• Gives sigmoid rather than hyperbolic kinetics, as in haemoglobin

Intermediate: covalent modification (seconds to minutes)

• Phosphorylation by kinases and dephosphorylation by phosphatases, the commonest mechanism and the endpoint of most hormone signalling
• Zymogen activation by proteolysis, used where the enzyme would be dangerous inside the cell: pepsinogen, trypsinogen, and the coagulation cascade

Slow: change in enzyme quantity (hours to days)

• Altered transcription, as with cortisol inducing gluconeogenic enzymes or phenobarbital inducing cytochrome P450
• Altered degradation

Compartmentalisation is a fourth mechanism: keeping fatty acid synthesis in the cytoplasm and oxidation in the mitochondrion prevents a futile cycle.

Reciprocal control is a recurring theme: the same phosphorylation event activates glycogen phosphorylase and inhibits glycogen synthase, so breakdown and synthesis can never run simultaneously.