bis-Allylic hydroxylation of linoleic acid and arachidonic acid by human hepatic monooxygenases.
[14C]Linoleic acid was incubated with human liver microsomes and NADPH and biosynthesis of allylic hydroxy fatty acids was investigated. 11-Hydroxy-9Z,12Z-octadecadienoic acid (11-HODE), 9-hydroxy-10E,12Z-octadecadienoic acid (9-HODE), 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE) and 14-hydroxy-9Z,12Z-octadecadienoic acid were identified. 9-HODE and 13-HODE were formed with stereoselectivity (80% R) provided that 11-HODE was prevented from decomposing to 9(R,S)-HODE and 13(R,S)-HODE by extractive isolation at pH 5-6. Human hepatic microsomes metabolized [14C]arachidonic acid to many products, including 13-HETE and small amounts of 15-HETE (> 90% R), 11-HETE (59% R) and 12-HETE (> 90% R). Hepatic microsomes of untreated rats metabolized [14C]linoleic acid to 11-HODE as a major product, but significant formation of 11-HODE by purified cytochrome P-450 (P450) (CYP1A1, CYP2B1, CYP2B4, CYP2E1, CYP3A6 and CYP4A1) in a reconstituted system could not be detected, indicating that 11-HODE might be formed by other and constitutive P450 isozymes.
Oliw
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Department of Pharmaceutical Biosciences, Uppsala University Biomedical Centre, Sweden.
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D006900:Hydroxylation; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000096:biosynthesis* / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D006893:Hydroxyeicosatetraenoic Acids; D008041:Linoleic Acids; C080024:11-hydroxy-9,12-octadecadienoic acid; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System; D019787:Linoleic Acid