Mechanism of enzyme action
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This document discusses the mechanisms of enzyme action, emphasizing their role as catalysts that accelerate chemical reactions without permanent changes. It covers two primary perspectives: thermodynamic changes, where enzymes lower activation energy for the transition state, and processes at the active site, involving four mechanisms: acid-base catalysis, covalent catalysis, catalysis by proximity and orientation, and catalysis by bond strain. Each mechanism offers insight into how enzymes enhance reaction rates and facilitate biochemical processes.
Mechanism of enzyme action
- 1. Mechanism of enzyme action Namrata Chhabra M.D.Biochemistry 15-May-20 Mechanism of enzyme action 1
- 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 15-May-20 Mechanism of enzyme action 2
- 3. 15-May-20 Mechanism of enzyme action 3 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 15-May-20 Mechanism of enzyme action 4
- 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‡. 15-May-20 Mechanism of enzyme action 5
- 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. 15-May-20 Mechanism of enzyme action 6
- 7. 15-May-20 Mechanism of enzyme action 7 1) Thermodynamic changes
- 8. 15-May-20 Mechanism of enzyme action 8 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. 15-May-20 Mechanism of enzyme action 9 1) Thermodynamic changes
- 10. Thermodynamic changes-overview 15-May-20 Mechanism of enzyme action 10
- 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 15-May-20 Mechanism of enzyme action 11
- 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 15-May-20 Mechanism of enzyme action 12
- 13. Reaction catalyzed by Lactate dehydrogenase 15-May-20 Mechanism of enzyme action 13
- 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. 15-May-20 Mechanism of enzyme action 14
- 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. 15-May-20 Mechanism of enzyme action 15
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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 15-May-20 Mechanism of enzyme action 17
- 18. Catalysis by proximity and orientation 15-May-20 Mechanism of enzyme action 18
- 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 15-May-20 Mechanism of enzyme action 19
- 20. Catalysis by bond strain 15-May-20 Mechanism of enzyme action 20
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- 22. Thank you 15-May-20 Mechanism of enzyme action 22