Proceedings of the National Academy of Sciences · 1982 · 154 citations · 15 references
Life SciencesBiochemistryPharmacologyCellular MetabolismEnzymologyMetabolismCytochrome P450 EnzymesCytochrome P450-mediated MetabolismOxidative MetabolismArachidonic Acid MetabolitesCytochrome P450-mediated OxidationFatty Acid Methyl EstersFatty AcidsHydroxy Fatty AcidsNadph-dependent EnzymesRat Liver MicrosomesUnsaturated Fatty Acids
Arachidonic acid is oxidized by a NADPH-dependent oxygenase of rat liver microsomes to a number of oxygen-containing products, which can be resolved by HPLC. Several of these products have been purified and characterized. They exhibit an absorbance in the UV region of the spectrum that has a maximum at approximately 235 nm, indicative of the presence of a conjugated diene function. Mass spectral analysis of the trimethylsilyl ether derivatives of the methyl esters of the hydrogenated and nonhydrogenated metabolites shows that they are the 9-, 11-, 12-, and 15-monohydroxy derivatives of arachidonic acid, the hydroxyicosatetraenoic acids (HETEs). Their UV absorbance and chromatographic properties suggest that these products possess cis,transdiene geometry characteristic of HETEs isolated from other mammalian sources. THe isolation of these isomeric HETEs suggests that cytochrome P-450 may play a role in the oxidative metabolism of arachidonic acid to physiologically and pharmacologically important hydroxylated unsaturated fatty acids.
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