How Do Proteins Work?

15.11.05

Kinetics:
• More complex relationship with substrate concentration.
• Characteristic hyperbolic shape.
• Michaelis-Menten equation
v0 = vmax [S]/Km [S]
Km = Michaelis constant - concentration at which substrate at 50% velocity.
• By modifying Michaelis-Menten equation, various plots can be obtained which enable Km and vmax to be determined.

Enzyme inhibition:
• Activity decreased by specific inhibitors.
• 1. Irreversible - inactivation eg. binding of DIFP to active site Ser of serine proteases.
2. Reversible.
a) Competitive - usually structurally related to substrate, therefore bind to active site and increase Km but do not affect v max for reaction. Inhibition overcome by addition of more substrate.
b) Non-competitive - bind to site distinct from active site, but close enough to interfere with catalytic process. vmax deceased; Km not affected.
• Enzymes often inhibited by substrate or product of reaction. Usually occurs at second (allosteric) site on enzyme and hence in non-competitive inhibition.
• Allosteric inhibition found between product of pathway and controlling (first committed) enzyme of that pathway.
• Inhibition may also be covalent - via phosphorylation controlled by hormones.

Enzymes as targets for drugs:
• Angiotensin is agonist for patients with high blood pressure.
• Angiotensin II, vasoconstrictor.