Biosynthesis of epoxyeicosatrienoic acids varies between polymorphic CYP2C enzymes
作者： Mia Sandberg Lundblad , Katarina Stark , Erik Eliasson , Ernst Oliw , Anders Rane
DOI: 10.1016/J.BBRC.2004.12.116
关键词:
摘要: Arachidonic acid is oxidized by cytochromes P450 2C (CYP2C) to epoxyeicosatrienoic acids (EETs), possessing vasoactive properties, with 11,12-EET as the endothelium derived hyperpolarization factor. Genetic variants of CYP2C enzymes have altered drug metabolizing capacity. Our primary aim was determine whether EET biosynthesis differed in human liver microsomes known genotypes. Human (n = 25) different genotypes or yeast-expressed were used. Analysis metabolites performed liquid chromatography/mass spectrometry. Samples genotyped CYP2C8*3/*3/CYP2C9*2/*2 exhibited a 34% (p < 0.05) decreased biosynthesis, compared other CYP2C8/CYP2C9 haplotypes. Inhibition experiments suggested CYP2C8 and CYP2C9 be predominant catalysts EETs. We found no differences between three recombinantly expressed variants, but CYP2C8.1 had lower K(m) than these isoforms. In conclusion, there are genetic CYP2C-dependent oxidation arachidonic metabolites, which relevance cardiovascular pathophysiology still unclear.
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