Metabolism of 12(R)-hydroxyeicosatetraenoic acid by rat liver microsomes.
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 dihydroxyeicosatetraenoic 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.
Jajoo
H K
HK
Department of Chemistry, Vanderbilt University, Nashville, TN.
Capdevila
J H
JH
Falck
J R
JR
Bhatt
R K
RK
Blair
I A
IA
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D006900:Hydroxylation; D015289:Leukotrienes / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet
D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid