This document discusses two types of enzyme catalysis: covalent and electrostatic. Covalent catalysis involves the transient formation of a covalent bond between an enzyme's nucleophilic group (such as an amino acid side chain) and an electrophilic group on the substrate. This is exemplified by the decarboxylation of acetoacetate through Schiff base formation with a lysine residue. Electrostatic catalysis enhances reaction rates through the arrangement of charged groups within the enzyme's active site to stabilize transition states. The local low dielectric environment of the active site strengthens electrostatic interactions.

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

4. 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.

5. Covalentcatalysis:
 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 ofacetoacetate

6. Nucleophilic reactions:

7. Decarboxylation of
acetoacetate:

9. 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.

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

11. 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.

12. 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

13. 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 .