Journal
BIOCHEMISTRY
Volume 50, Issue 21, Pages 4402-4410Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bi2002289
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Funding
- Israel Academy of Sciences and Humanities
- Azrieli Foundation
- Kahn Center for System Biology
- ERC [260392]
- Israel Science Foundation [750/09]
- Mr. and Mrs. Yossie Hollander and Miel de Botton Aynsley funds
- European Research Council (ERC) [260392] Funding Source: European Research Council (ERC)
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The kinetic parameters of enzymes are key to understanding the rate and specificity of most biological processes. Although specific trends are frequently studied for individual enzymes, global trends are rarely addressed. We performed an analysis of k(cat) and K-M values of several thousand enzymes collected from the literature. We found that the average enzyme exhibits a k(cat) of similar to 10 s(-1) and a k(cat)/K-M of similar to 10(5) s(-1) M-1, much below the diffusion limit and the characteristic textbook portrayal of kinetically superior enzymes. Why do most enzymes exhibit moderate catalytic efficiencies? Maximal rates may not evolve in cases where weaker selection pressures are expected. We find, for example, that enzymes operating in secondary metabolism are, on average, similar to 30-fold slower than those of central metabolism. We also find indications that the physicochemical properties of substrates affect the kinetic parameters. Specifically, low molecular mass and hydrophobicity appear to limit K-M optimization. In accordance, substitution with phosphate, Colt, or other large modifiers considerably lowers the K-M values of enzymes utilizing the substituted substrates. It therefore appears that both evolutionary selection pressures and physicochemical constraints shape the kinetic parameters of enzymes. It also seems likely that the catalytic efficiency of some enzymes toward their natural substrates could be increased in many cases by natural or laboratory evolution.
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