Enzyme Activators Substances that bind with the enzyme

Enzyme Activators Substances that bind with the enzyme and increase its activity

Effect of Activators on rate of Enzyme catalyzed reactions

• Some Enzymes require activators to increase the rate of reaction. • Activators cause activation of Enzyme-catalyzed reaction by either altering the velocity of the reaction or the equilibrium reached or both. Essential activators: • Essential for the reaction to proceed. • These are recognized as substrate that is not changed in the reaction e. g. metal ion such as Mg++for kinases. Non essential activators: • Activator may act to promote a reaction which is capable of proceeding at a appreciable rate in the absence of activator.

Enzyme Inhibitors

Enzyme Inhibitors Substances that bind with the enzyme and decrease its activity

Enzyme inhibitors Irreversible E+ I EI Competitive Reversible E+I Uncompetitive EI Noncompetitive

Inhibition of Enzyme Activity Irreversible Inhibition E + I →E –IE does not regain activity. • This inhibitor cannot be removed by dialysis or other means. • Inhibition increases with time. Examples of irreversible inhibitors CN inhibits xanthine oxidase. Nerve gas inhibits cholinesterase. Iodoacetamide, heavy metal ions (Hg++), oxidizing agents.

Reversible Inhibition E + I↔E –I • Enzyme & Inhibitor are bind by non-covalent bonds. • E –I complex can be dissociated by dilution and dialysis Types of reversible inhibitors: (i) Competitive (ii) Non-competitive (iii) Uncompetitive

Competitive inhibition • Inhibitor binds with free Enzyme at active site • Inhibitor resembles Substrate and competes with Substrate to bind the active site. E + I ↔ E + S ↔ES ES ↔EI [S] • Inhibitor is not changed during reaction. Dissociation constant (Ki) Ki = [E] [I]/ [EI] • Competitive Inhibition do not change Vmax so when Substrate is increased it removes Inhibitor from active site and the inhibition is reversed. • Increase Km (decrease affinity of E for S). E + I →E –IE does not regain activity.

Examples of reversible inhibitors • Inhibition of succinate dehydrogenase by malonate. • Inhibition of methanol dehydrogenase by ethanol.

Non-competitive Inhibition • Inhibitor binds to a site other than the active site. • Inhibitor can bind free E and ES complex. • Inhibitor does not resemble Substrate. • No competition between Inhibitor and Substrate. • Increasing Substrate does not decrease inhibition. • Non-competitive Inhibition decreases Vmax, but does not alter Km.

Uncompetitive Inhibition • The Inhibitors does not bind free Enzyme, but binds E-S complex and forms an inactive E-S-I complex which cannot give normal product. ES + I ↔ESI • Inhibitor affects both Vmax and Km.