covalent and electrostatic catalysis

enzyme catalysis covalent and electrostatic catalysis mechanisms.

1. Submitted by, t. soundarya p19bc004 I m.sc biochemistry Covalent and electrostatic catalysis

2. INTRODUCTION: Enzymes are biocatalyst. They increases the rate of chemical reactions taking place within living cells without themselves suffering any overall change. The reactants of enzyme- catalysed reactions are termed substrates and each enzyme quit specific in character, acting on a particular substrate to produce particular product

3. Catalysis: A catalyst accelerates a chemical reactions without changing its extent and can be removed unchanged from amongst the end products of the reaction. It has no overall thermodyanamic effect: the amount of energy liberated or taken up when a reaction has been completed will be the same whether a catalyst is present or not.

4. Covalent catalysis: Covalent Catalysis accelerates reaction rates through the transient formation of a catalyst-substrate covalent bond. Usually, nucleophilic group on enzyme attacks an electrophilic group on the substrate = nucleophilic catalysis Example: decarboxylation of acetoacetate

5. Nucleophilic reactions:

6. Decarboxylation of acetoacetate :

7. Certain Amino Acid Side Chains and Coenzymes Can Serve as Covalent Catalysts Enzymes commonly employ covalent catalytic mechanisms as is indicated by the large variety of covalently linked enzyme–substrate reaction intermediates that have been isolated.For example,the enzymatic decarboxylation of acetoacetate proceeds, much as described above, through Schiff base formation with an enzyme Lys residue’s ε-amino group. The covalent intermediate,in this case, has been isolated through NaBH4 reduction of its imine bond to an amine,thereby irreversibly inhibiting the enzyme .

8. Nucleophilicity of a substance is related to its basicity :

9. Continued.. Other enzyme functional groups that participate in covalent catalysis include the imidazole moiety of His, the thiol group of Cys , the carboxyl function of Asp, and the hydroxyl group of Ser.In addition,several coenzymes, most notably thiamine pyrophosphate (Section 17-3Ba) and pyridoxal phosphate (Section 26-1Aa), function in association with their apoenzymes mainly as covalent catalysts.

10. Electrostatic Catalysis The binding of substrate generally excludes water from an enzyme’s active site.The local dielectric constant of the active site therefore resembles that in an organic solvent, where electrostatic interactions are much stronger than they are in aqueous solutions . The charge distribution in a medium of low dielectric constant can greatly influence chemical reactivity. Thus,as we have seen, the pK’s of amino acid side chains in proteins may vary by several units from their nominal values because of the proximity of charged groups

11. Continued.. Although experimental evidence and theoretical analyses on the subject are still sparse,there are mounting indications that the charge distributions about the active sites of enzymes are arranged so as to stabilize the transition states of the catalyzed reactions. Such a mode of rate enhancement,which resembles the form of metal ion catalysis discussed above,is termed electrostatic catalysis.Moreover,in several enzymes,these charge distributions apparently serve to guide polar substrates toward their binding sites so that the rates of these enzymatic reactions are greater than their apparent diffusion-controlled limits .