Enzymatic Rate Enhancements


Enzymatic rate enhancements arise from the unmatched ability of enzymes to stabilise the transition states of the reactions that they catalyse. Comparison of rate constants of an enzyme‐catalysed reactions, that is, kcat and kcat/Km, to that of the corresponding reaction in the absence of the enzyme, that is, kN, provides quantitative measures of enzyme catalytic power. Moreover, the ratio of kN to kcat/Km provides a quantitative measure of transition state stabilisation effected by enzymes, which in turn motivates the development of ultrapotent transition state analogue enzyme inhibitors. The purpose of this article is to discuss the magnitude and mechanistic origins of enzymatic rate enhancements. Selected enzymes are described that manifest a wide range of rate enhancements and corresponding catalytic strategies. Factors that affect the evolution of enzyme catalytic power are presented.

Key Concepts:

  • A catalyst is a species that accelerates a chemical reaction without affecting the equilibrium constant of the reaction.

  • Enzymes are catalysts that accelerate chemical reactions that are necessary for life.

  • The quantitative degree to which an enzyme accelerates a chemical reaction is a measure of the catalytic power of the enzyme.

  • Enzymes derive their catalytic power from their marked abilities to stabilise the transition state(s) of the reactions that they catalyse.

  • Enzymic catalytic power is quantitated as the ratio of rate constants of enzyme‐catalysed reactions to the rate constants for the corresponding reactions in the absence of enzyme.

  • Enzymes whose catalytic power is highly evolved operate at the speed limit of biological catalysis; that is, they are diffusion controlled.

Keywords: catalytic acceleration; transition state stabilisation; enzyme catalytic power; diffusion control; enzyme mechanisms; enzyme catalysis

Figure 4.

Transition state stabilisation and transition state binding in a double displacement enzyme mechanism. Free energy changes in eqn that correspond to the thermodynamic cycle of Scheme are shown in blue. The solid black curve plots the energetics of the enzyme reaction when [A]≪Km. The dashed black line shows how the free energy of the E+A state changes when [A]≫Km. The solid green curve plots the energetics of the nonenzymic reaction.

Figure 5.

Free‐energy diagram for TIM catalysis.



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Further Reading

A subject of considerable current interest is the role of protein dynamics in enzyme function and the expression of enzyme catalytic power, especially as gauged through experiments that support tunneling in enzyme-catalyzed hydron transfers. The reader is referred to the following reference for an insightful review of this topic: a) Nagel ZD and Klinman JP (2006) Tunneling and dynamics in enzymatic hydride transfer. Chemical Reviews 106: 3095–3118; b) Klinman JP and Kohen A (2013) Hydrogen tunneling links protein dynamics to enzyme catalysis. Annual Review of Biochemistry 82: 471–496. See also Protein Structural Flexibility: Molecular Motions

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Quinn, Daniel M, and Sikorski, R Steven(Jul 2014) Enzymatic Rate Enhancements. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000717.pub3]