Abstract
[1-14C]Docosahexaenoic acid (n-3) was incubated at 37 degrees C for 30 min in the presence of rat liver microsomes and 1 mM NADPH. The products were isolated using organic solvent extractions, reverse phase, and normal phase high performance liquid chromatography. Isolates were identified using ultraviolet spectroscopy, capillary gas-liquid chromatography, and gas chromatography-mass spectrometry. The major metabolites were: 19,20-, 16,17-, 13,14-, 10,11-, and 7,8-dihydroxydocosapentaenoic acids, 22-hydroxydocosahexaenoic acid, and 21-hydroxydocosahexaenoic acid. The minor metabolites were 17-hydroxy-4,7,10,13,15,19-, 16-hydroxy-4,7,10,17,19-, 14-hydroxy-4,7,10,12,-16,19-, 13-hydroxy-4,7,10,14,16,19-, 11-hydroxy-4,7,9,13,16,19-, 10-hydroxy-4,7, 11,13,16,19-, 8-hydroxy-4,6,10,13,16,19-, and 7-hydroxy-4,8,10,13,16,19 -docosahexaenoic acids. These metabolites of docosahexaenoic acid resulted from four distinct classes of oxidation, omega-hydroxylations, (omega-1)-hydroxylations, epoxidations, and lipoxygenase-like hydroxylations. The similarity of these product profiles to those reported for comparable microsomal incubations with other essential fatty acids suggest that microsome cytochrome P-450 monooxygenases were involved.
Highlights
37 O C for 30 min in the presence of rat liver micro- genases into (w-1)-oxo-fatty acids [15,16,17]
Such dicarboxylic acids are produced by the reaction sequence: primary alcohol to aldehyde to carboxylic acid [1,2,4, 5]
The abbreviations used are: w or n, the methyl terminus of a fatty acid; x:y, n is the number of carbons and y the number of double bonds in a fatty acid; P-450, microsomalcytochrome P-450; C, vehicular control; BNF, p-naphthoflavone (5,6-benzoflavone);PB, phenobarbital; HPLC, high performance liquid chromatography; NP, normal phase; RP, reverse phase; ODs, octadecylsilane [41]; GC, gasliquid chromatography; HETE, hydroxyeicosatetraenoic acid
Summary
The average liver weights from C, BNF, and PB-treated rats were 9.30, 9.50, and 12.37 g, respectively. These numbers represent average values from 2-6 duplicate ence of 1 mM NADPH. A t least 23 radioactive peaks were resolved from 22:6 by revealed high mass ions at 520 (M), 489 (M - OCH,), and RP-HPLC (Fig. 1). Compounds VI and VI1were base-line separated from each other by NP-HPLC usingisopropyl alcohokhexane (0.5:lOO) After isolation it wasfound that they had an identical UV spectrum (Fig. 2B) whichwas different from that of GroupA metabolites, which contained a shoulder at 215 nm (Fig. 24).
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