PMID: 9643352Jun 27, 1998Paper

Involvement of cytochrome P450 2E1 in the (omega-1)-hydroxylation of oleic acid in human and rat liver microsomes.

Journal of Lipid Research
F AdasY Amet

Abstract

In vitro techniques have been used to investigate the nature of microsomal cytochrome P450 involved in the metabolism of oleic acid, a physiological monounsaturated fatty acid. Like lauric acid, which is currently used as a model substrate of fatty acid metabolism, the alkyl chain of oleic acid is hydroxylated on its omega and (omega-1) carbons. The identity of these hydroxylated metabolites was ascertained by GC/MS and LC/MS. The omega/omega-1 ratio of oleic acid metabolites (1.22+/-0.01) was found to be similar to that obtained with lauric acid in rat liver microsomes (1.10+/-0.02), while in human liver microsomes this ratio was 0.75+/-0.5 for lauric acid and 5.2+/-2.6 for oleic acid. After treatment of rats with ethanol or clofibrate, inducers of CYP2E1 and CYP4A, respectively, the hydroxylations of oleic acid were shown to be less inducible than those of lauric acid. Five in vitro approaches were used to identify the P450 isoform(s) responsible for the microsomal (omega-1)-hydroxylation of oleic acid: effect of various inducers in rats, correlation studies between specific P450 catalytic activities in a panel of 25 human liver microsomes, chemical inhibitions, immuno-inhibitions and metabolism by cDNA-expressed human P450 e...Continue Reading

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