Enzyme inhibition and regulation

Inhibitors slow down enzyme reactions.

Irreversible inhibitors bind tightly and do not come off. Penicillin blocks the bacterial enzyme transpeptidase, so bacteria cannot build their cell walls and die. Aspirin blocks cyclooxygenase, reducing inflammation and pain.

Reversible inhibitors come off easily. There are three types:

• Competitive: the inhibitor looks like the substrate and competes with it for the active site. The enzyme holds either the substrate (ES) or the inhibitor (EI), never both. Adding plenty of substrate wins the competition, so Vmax stays the same, but more substrate is needed to reach half speed: Km rises.
• Non-competitive: the inhibitor binds somewhere else on the enzyme, to E or to ES, forming an ESI complex that makes no product. Adding more substrate does not help. Vmax falls; Km stays the same.
• Uncompetitive: the inhibitor binds only to the ES complex. Both Km and Vmax change, and extra substrate does not overcome it.

Allosteric enzymes have, besides their active sites, extra regulatory sites. Molecules binding there change how strongly the enzyme holds its substrate, switching it up or down. Their rate curve is S-shaped (sigmoidal), not a hyperbola. Allosteric enzymes are the main control points of metabolic pathways.