Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 50 (21), 4402-10

The Moderately Efficient Enzyme: Evolutionary and Physicochemical Trends Shaping Enzyme Parameters

Affiliations

The Moderately Efficient Enzyme: Evolutionary and Physicochemical Trends Shaping Enzyme Parameters

Arren Bar-Even et al. Biochemistry.

Abstract

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 ~0 s(-1) and a k(cat)/K(M) of ~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, ~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, CoA, 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.

Similar articles

See all similar articles

Cited by 173 PubMed Central articles

See all "Cited by" articles

Publication types

LinkOut - more resources

Feedback