Enzyme Inhibition

Inhibitors

• Any molecule that binds to an enzyme and inhibits its function (slows the rate of reaction)
• The stronger the inhibitor, the lower concentration needed to impact rate
• Two types:

• Reversibly inactivates enzymes
• Inhibitor binds non-covalently to the enzyme
• Two methods of inhibition:
• In competitive inhibition, reversion occurs through increasing amount of substrate (out-competes for active site)
• In non-competitive inhibition, effects are reversed by lowering inhibitor concentration

• Inhibitor covalently binds to the active site of the enzyme
• Inhibitor closely resembles the substrate or a transition state

Competitive Inhibition of Enzymes

• Inhibitors which compete with the substrate for binding to the active site
• Reduces the rate at which the enzyme binds the substrate
• Can be reversed through increasing amount of substrate (out-competes for active site)
• If reversible, it does not change Vmax, but increases Km

Non-Competitive Inhibition of Enzymes

• Binds to a site on the enzyme somewhere other than the active site
• Effects are reversed by lowering inhibitor concentration
• Results in a lower Vmax, but Km is unchanged

Effects of inhibitors on Reaction Rate

• In Michaelis-Mentan plots the blue lines (number 2) represent the curve in the presence of the designated inhibitor
• *These are for reversible inhibitors, but the effects of irreversible inhibitors are the same as what is seen for Non-Competitive inhibitors*
• Irreversible inhibitors compete for the active site, but effects can only be diminished through decreasing the concentration of inhibitor