METABOLISM OF 12(R)-HYDROXYEICOSATETRAENOIC ACID BY RAT-LIVER MICROSOMES

被引:10
作者
JAJOO, HK
CAPDEVILA, JH
FALCK, JR
BHATT, RK
BLAIR, IA
机构
[1] VANDERBILT UNIV, DEPT PHARMACOL, NASHVILLE, TN 37232 USA
[2] VANDERBILT UNIV, DEPT CHEM, NASHVILLE, TN 37232 USA
[3] VANDERBILT UNIV, CTR MOLEC TOXICOL, NASHVILLE, TN 37232 USA
[4] VANDERBILT UNIV, DEPT MED, DIV NEPHROL, NASHVILLE, TN 37240 USA
[5] VANDERBILT UNIV, DEPT BIOCHEM, NASHVILLE, TN 37240 USA
[6] UNIV TEXAS, SW MED CTR, DEPT MOLEC GENET, DALLAS, TX 75230 USA
关键词
CYTOCHROME-P-450; EICOSANOID; METABOLISM; RAT LIVER MICROSOME; EPOXYGENASE;
D O I
10.1016/0005-2760(92)90177-W
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
The in vitro metabolism of 12(R)-hydroxyeicosatetraenoic acid was studied using freshly isolated rat liver microsomes. Ten metabolites were isolated and identified by a combination of ultraviolet spectroscopy and gas chromatography/mass spectrometry. The two major metabolites were dihdroxyeicosatetraenoic acids generated by omega/omega - 1 hydroxylation. Oxidation at C-5 resulted in the formation of four leukotriene-like compounds, two of which differed from leukotriene B4 in double-bond geometry alone. The other two differed from leukotriene B4 in olefin geometry and C-5 configuration. Epoxidation at the 14,15-olefin resulted in the formation of two diastereomeric epoxy alcohols, while C-16 hydroxylation gave two diastereomeric dihydroxyeicosatetraenoic acids.
引用
收藏
页码:110 / 116
页数:7
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