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

2. Effect of Activators on rate of Enzyme catalyzed reactions

3. 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.

6. Enzyme Inhibitors

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

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

9. 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.

10. 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

11. Competitive inhibition Inhibitor binds with free Enzyme at active site Inhibitor resembles Substrate and competes with Substrate to bind the active site. E + I ↔ EI ↔ ES E + S ↔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.

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

15. 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.

19. 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.