1. Enzymes Have properties shared by all catalysts Enhance the rates of both forward and reverse reactions so equilibrium is achieved more rapidly Position of equilibrium is unchanged Reduce activation energy Not permanently altered during the reaction Can act over and over again = catalytically Have unique properties Exhibit extreme substrate (reactant) specificity Exhibit reaction specificity, no side reactions Can couple reactions Can be regulated

2. Enzyme-catalyzed Reactions ES = Enzyme-substrate complex formed when substrates fit into the active site of the enzyme E + S ESE + P

3. Michaelis-Menten Theory v o = initial velocity, ignore reverse reaction, measure rate before P accumulates k 1 and k -1 represent rapid noncovalent association of substrate with enzyme’s active site k 2 = rate constant for the chemical conversion of S to P, the rate-limiting step v o = k 2 [ES] E + SESE + P k1k1 k2k2 k -1

5. Michaelis-Menten Theory Assumptions: v o = initial velocity, ignore reverse reaction [ES] is constant Conversion of S to P is rate-limiting, v o = k 2 [ES] E + SESE + P k1k1 k2k2 k -1 V max [S] V o = ------------- K m + [S]

6. Fig. 5.4 Michaelis-Menten Plot V max [S] V o = ------------- K m + [S]

7. K m = Michaelis constant Is a measure of the affinity of E for S k -1 + k 2 K m = k 1 Inverse relationship: when K m is small affinity is great

8. k cat = catalytic constant or turnover number Moles of S converted to P per second per mole of enzyme ( or active site) Inverse of k cat tells you how much time is required to convert one mole S to P

10. Fig. 5.6

11. Enzyme Regulation See both positive and negative regulation Small molecules interact with enzyme Can bind to E to affect binding of S to form ES Can bind to ES to affect conversion of S to P  Consider inhibitors first  reversible or irreversible inhibition  noncovalent vs. covalent interactions between E and I

12. Fig. 5.8

13. Fig. 5.9

14. Statins are competitive inhibitors of cholesterol synthesis

15. Fig. 5.9

16. Fig. 5.8

17. Fig. 5.11

19. Fig. 5.8

20. Fig. 5.12