Question

Carbonic anhydrase (CA) has a 25,000-fold higher activity (kcat = 106 s-1) than orotidine monophosphate decarboxylase (OMPD) (kcat 40 s-1). However, OMPD provides more than a 1010 higher "rate acceleration" than CA (Table). Explain how this is possible. Catalytic proficiencies of some enzymes Catalytic Nonenzymatic rate Enzymatic rate constant constant (kn in s-1) (kcat/Am in M-1s-1) proficiency Carbonic anhydrase 7 x 106 10-1 7 X 107 Chymotrypsin 4 x 10-9 9 x 107 2 X 1016 2 x 106 Chorismate mutase 10-5 2 x 1011 Triose phosphate 4 x 10-6 4 x 108 1014 isomerase Cytidine deaminase 10-10 3 x 106 3 x 1016 Adenosine deaminase 2 x 10-10 5 x 1016 107 Mandelate racemase 3 x 10-13 106 3 x 1018 b-Amylase 7 x 10-14 107 1020 Fumarase 10-13 109 1021 Arginine 9 x 10-16 106 1021 decarboxylase Alkaline phosphatase 3 x 107 10-15 3 x 1022 Orotidine 5'-phosphate 3 x 10-16 2 x 1023 6 x 107 decarboxylase

Answer 1

1) An enzyme should bind weakly the substrate in the ground state to enhance the rate of reaction, and also should have high affinity for altered substrate in transition state.

2) The ability to keep away from tight binding of the substrate in the ground state (ground state destabilization), the ground state and transition state should differ only to some extent in structure. This can be achieved by a reduction in the size of the substrate by steric hindrance.

3) These Steric effects are prominent in the action of OMPD, which produces largest rate enhancements. Therefore, OMPD provides more than 1010 rate acceleration than CA.