CYP2E1 metabolism of styrene involves allostery.

ABSTRACT: We are the first to report allosterism during styrene oxidation by recombinant CYP2E1 and human liver microsomes. At low styrene concentrations, oxidation is inefficient because of weak binding to CYP2E1 (K(s) = 830 μM). A second styrene molecule then binds CYP2E1 with higher affinity (K(ss) = 110 μM) and significantly improves oxidation to achieve a k(cat) of 6.3 nmol · min(-1) · nmol CYP2E1(-1). The transition between these metabolic cycles coincides with reported styrene concentrations in blood from exposed workers; thus, this CYP2E1 mechanism may be relevant in vivo. Scaled modeling of the in vitro-positive allosteric mechanism for styrene metabolism to its in vivo clearance led to significant deviations from the traditional model based on Michaelis-Menten kinetics. Low styrene levels

SUBMITTER: Hartman JH 

PROVIDER: S-EPMC3463823 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature