Enzymes are catalysts and increase the speed of a chemical reaction without themselves undergoing any permanent chemical change.

1. Mechanism of
enzyme action
Namrata Chhabra
M.D.Biochemistry
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2. General Mechanism of Action of Enzymes
• Enzymes are catalysts and increase the speed of a chemical reaction
without themselves undergoing any permanent chemical change.
• They are neither used up in the reaction nor do they appear as
reaction products.
• The basic enzymatic reaction can be represented as follows
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General Mechanism of Action of Enzymes

4. Mechanism of enzyme action
• Enzymes employ multiple mechanisms to facilitate catalysis. The
mechanism of action of enzymes can be explained by
two perspectives-
1) Thermodynamic changes
2) Processes at the active site
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5. 1) Thermodynamic changes
• A chemical reaction of substrate S to form
product P goes through a transition state S‡ that
has a higher free energy than does either S or P.
(The double dagger denotes a thermodynamic
property of the transition state).
• The difference in free energy between the
transition state and the substrate is called
the Gibbs free energy of activation or simply
the activation energy, symbolized by ∆G‡.
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6. 1) Thermodynamic changes
• All enzymes accelerate reaction rates by providing transition
states with a lowered G for formation of the transition states.
However, they may differ in the way this is achieved.
• The combination of substrate and enzyme creates a new reaction
pathway whose transition-state energy is lower than that of the
reaction in the absence of enzyme.
• The lower activation energy means that more molecules have the
required energy to reach the transition state.
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1) Thermodynamic changes

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1) Thermodynamic changes

9. Decreasing the activation barrier is
analogous to lowering the height of
a high-jump bar; more athletes will
be able to clear the bar.
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1) Thermodynamic changes

10. Thermodynamic changes-overview
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11. 2) Processes at the active site
• Enzymes use various combinations of four general mechanisms to
achieve dramatic catalytic enhancement of the rates of chemical
reactions.
• These are as follows:
• Acid base catalysis
• Covalent catalysis
• Catalysis by proximity and orientation
• Catalysis by bond strain
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12. Acid- base catalysis
• Mostly undertaken by oxidoreductases.
Usually, at the active site, either histidine is
present which acts both as a proton donor
and proton acceptor.
• At times aspartic acid, glutamic acid and
cysteine residues are also present which
participate in Hydrogen transfer reactions
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13. Reaction catalyzed by Lactate dehydrogenase
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14. Covalent catalysis
• In catalysis that takes place by covalent mechanisms, the substrate is
oriented to active sites on the enzymes in such a way that a covalent
intermediate forms between the enzyme or coenzyme and the substrate.
• Examples of this mechanism- digestive enzymes (trypsin, chymotrypsin,
and elastase) and several enzymes of the blood clotting cascade.
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15. Covalent catalysis
• Covalent catalysis introduces a new reaction pathway whose
activation energy is lower—and therefore is faster—than the reaction
pathway in homogeneous solution.
• The chemical modification of the enzyme is, however, transient.
• On completion of the reaction, the enzyme returns to its original
unmodified state.
• Its role thus remains catalytic.
• Covalent catalysis is particularly common among enzymes that
catalyze group transfer reactions.
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17. Catalysis by proximity and orientation
• For molecules to react, they must come within bond-forming distance
of one another.
• The higher their concentration, the more frequently they will
encounter one -another and the greater will be the rate of their
reaction.
• When an enzyme binds substrate molecules at its active site, it
creates a region of high local substrate concentration.
• Enzyme-substrate interactions orient reactive groups and bring them
into proximity with one another
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18. Catalysis by proximity and orientation
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19. Catalysis by bond strain
• The induced structural rearrangements that take place with the
binding of substrate and enzyme ultimately produce strained
substrate bonds, which more easily attain the transition state.
• Enzymes that catalyze lytic reactions that involve breaking a covalent
bond typically bind their substrates in a conformation slightly
unfavorable for the bond that will undergo cleavage.
• The resulting strain stretches or distorts the targeted bond,
weakening it and making it more vulnerable to cleavage
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20. Catalysis by bond strain
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22. Thank you
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