Stereochemistry of the Biotransformation of 1-Hexene and 2-Methyl-1-hexene with Rat Liver Microsomes and Purified P450s of Rats and Humans

• Published in: Chemical research in toxicology Vol. 11; no. 12; pp. 1487 - 1493
• Main Authors: Chiappe, Cinzia, De Rubertis, Antonietta, Amato, Giada, Gervasi, Pier Giovanni
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.12.1998
• Subjects: Alkenes - chemistry; Alkenes - metabolism; Animals; Biotransformation; Catalysis; Cytochrome P-450 Enzyme System - metabolism; Humans; Hydrolysis; In Vitro Techniques; Kinetics; Male; Microsomes, Liver - enzymology; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Stereoisomerism
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx980170d

The epoxidation of 1-hexene (1a) and 2-methyl-1-hexene (1b), two hydrocarbons present in the ambient air as pollutants, is catalyzed by some human and rat P450 enzymes. The enantioselectivities of these processes, when the reactions were carried out using rat and human liver microsomal preparations, were modest and dependent on both P450 composition and substrate concentrations. Various P450 isoforms (rat P450 2B1 and human P450 2C10 and 2A6) catalyzed the double bond oxidation of 1a and 1b with different product enantioselectivities. In the case of 1a, a moderately enantioselective hydroxylation at the allylic C(3) with the formation of 1-hexen-3-ol (4a) by microsomes from control or preinduced rats was also observed. The oxidation of this metabolite was, in turn, catalyzed by rat liver microsomes and mainly by rat P450 2C11, leading exclusively to the formation of 1-hexen-3-one, with no double bond epoxidation being observed. The stereochemical course of the microsomal epoxide hydrolase-catalyzed hydrolysis of the epoxy alcohols, threo-(±)- and erythro-(±)-1,2-epoxyhexan-3-ol, theoretically expected to be formed from 4a, has been investigated.