bis-Allylic hydroxylation of linoleic acid and arachidonic acid by human hepatic monooxygenases

Biochim Biophys Acta. 1993 Feb 24;1166(2-3):258-63. doi: 10.1016/0005-2760(93)90106-j.


[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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acid / metabolism*
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 Enzyme System / metabolism*
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Hydroxyeicosatetraenoic Acids / biosynthesis*
  • Hydroxylation
  • Linoleic Acid
  • Linoleic Acids / biosynthesis*
  • Linoleic Acids / metabolism*
  • Liver / metabolism*
  • Male
  • Microsomes, Liver / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stereoisomerism


  • Hydroxyeicosatetraenoic Acids
  • Linoleic Acids
  • 11-hydroxy-9,12-octadecadienoic acid
  • Arachidonic Acid
  • Cytochrome P-450 Enzyme System
  • Linoleic Acid