Cytochrome P-450-dependent oxidation of arachidonic acid to 16-, 17-, and 18-hydroxyeicosatetraenoic acids.
Incubation of rat liver microsomal fractions with arachidonic acid in the presence of NADPH results in the formation of three novel monohydroxylated fatty acid metabolites. Utilizing chromatographic and mass spectral techniques, these metabolites have been identified as 16-, 17-, and 18-hydroxyeicosatetraenoic acids. The NADPH-dependent microsomal metabolism of arachidonic acid to 16-, 17-, 18-, and 19-hydroxyeicosatetraenoic acids is induced after animal treatment with beta-naphthoflavone. Reconstitution of the arachidonic acid oxygenase utilizing individual purified cytochrome P-450 enzymes demonstrates regioselectivity, controlled by the protein catalyst, for the hydroxylation of the sp3 carbon atoms adjacent to the methyl end of the fatty acid.
Falck
J R
JR
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
Lumin
S
S
Blair
I
I
Dishman
E
E
Martin
M V
MV
Waxman
D J
DJ
Guengerich
F P
FP
Capdevila
J H
JH
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000302:isolation & purification / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis* / Q000302:isolation & purification; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; D003577:Cytochrome P-450 Enzyme System