BIS-ALLYLIC HYDROXYLATION OF LINOLEIC-ACID AND ARACHIDONIC-ACID BY HUMAN HEPATIC MONOOXYGENASES

被引:30
作者
OLIW, EH
机构
[1] Department of Pharmaceutical Biosciences, Uppsala University Biomédical Centre
关键词
LIVER METABOLISM; ESSENTIAL FATTY ACID; MASS SPECTROMETRY; CYTOCHROME-P-450; PHENOBARBITAL;
D O I
10.1016/0005-2760(93)90106-J
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
[C-14]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 [C-14]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 [C-14]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.
引用
收藏
页码:258 / 263
页数:6
相关论文
共 22 条
[1]  
BLIGH EG, 1959, CAN J BIOCHEM PHYS, V37, P911
[2]  
BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3
[3]   METABOLISM OF 18-2(N-6), 18-3(N-3), 20-4(N-6) AND 20-5(N-3) BY THE FUNGUS GAEUMANNOMYCES-GRAMINIS - IDENTIFICATION OF METABOLITES FORMED BY 8-HYDROXYLATION AND BY W2 AND W3 OXYGENATION [J].
BRODOWSKY, ID ;
OLIW, EH .
BIOCHIMICA ET BIOPHYSICA ACTA, 1992, 1124 (01) :59-65
[4]   ABSOLUTE-CONFIGURATION OF THE HYDROXYEICOSATETRAENOIC ACIDS (HETES) FORMED DURING CATALYTIC OXYGENATION OF ARACHIDONIC-ACID BY MICROSOMAL CYTOCHROME-P-450 [J].
CAPDEVILA, J ;
YADAGIRI, P ;
MANNA, S ;
FALCK, JR .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 141 (03) :1007-1011
[5]   INFLUENCE OF A FIBRIC ACID TYPE OF HYPOLIPIDEMIC AGENT ON THE OXIDATIVE-METABOLISM OF ARACHIDONIC-ACID BY LIVER MICROSOMAL CYTOCHROME-P-450 [J].
CAPDEVILA, J ;
KIM, YR ;
WIXTROM, CM ;
FALCK, JR ;
MANNA, S ;
ESTABROOK, RW .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1985, 243 (01) :8-19
[6]  
CAPDEVILA J, 1983, BIOCHEM BIOPH RES CO, V111, P644
[7]  
COOK HW, 1991, BIOCH LIPIDS LIPOPRO, V20, P141
[8]  
DEMONTELLANO PRO, 1986, STRUCTURE MECHANISM, P217
[9]  
FALCK JR, 1990, J BIOL CHEM, V265, P10244
[10]   LINOLEIC-ACID METABOLISM IN THE RED ALGA LITHOTHAMNION-CORALLIOIDES - BIOSYNTHESIS OF 11(R)-HYDROXY-9(Z), 12(Z)-OCTADECADIENOIC ACID [J].
HAMBERG, M ;
GERWICK, WH ;
ASEN, PA .
LIPIDS, 1992, 27 (07) :487-493