Oxygenation of linolenic and linoleic acid to novel vicinal dihydroxy acids by hepatic microsomes of the rabbit.
[14C] Linolenic acid (18: omega 3) and [14C] linoleic acid (18:2 omega 6) were incubated with hepatic microsomes of the rabbit in the presence of NADPH (1 Mm) for 15 min at 37 degrees C. The products were extracted and purified by high performance liquid chromatography. The major metabolites of linolenic and linoleic acid were identified by capillary gas chromatography mass spectrometry as 15,16-dihydroxy-9,12-octadecadienoic acid, 12,13-dihydroxy-9,15-octadecadienoic acid and 9,10-dihydroxy-12,15-octadecadienoic acid and as 12,13-dihydroxy-9-octadecaenoic acid and 9,10-dihydroxy-12-octadecaenoic acid, respectively. The results were confirmed by comparison with mass spectra of the authentic compounds. These metabolites are presumably formed by cytochrome P-450 catalyzed epoxidation of the omega 3, omega 6 and omega 9 double bonds, followed by enzymatic hydrolysis to 1,2-diols. The ratio of omega 3, omega 6 and omega 9 oxygenated metabolites of linolenic acid was approximately 2:1:1 and the ratio of the omega 6 and omega 9 metabolites of linoleic acid was 2:1, indicating that the double bond closest the omega end is most easily oxygenated.
D000818:Animals; D008401:Gas Chromatography-Mass Spectrometry; D006880:Hydroxy Acids / Q000378:metabolism; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism*; D008042:Linolenic Acids / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D011817:Rabbits; D017962:alpha-Linolenic Acid
D006880:Hydroxy Acids; D008041:Linoleic Acids; D008042:Linolenic Acids; D017962:alpha-Linolenic Acid; D009249:NADP; D019787:Linoleic Acid