omega-Hydroxylation of 15-hydroxyeicosatetraenoic acid by lung microsomes from pregnant rabbits.
15-Hydroxyeicosatetraenoic acid (15-HETE) was converted by lung microsomes from pregnant rabbits to a polar metabolite that was identified by mass spectrometry as the 15,20-dihydroxyeicosatetraenoic acid. The formation of the 20- or omega-hydroxylated product was NADPH dependent, with a specific activity of 1.87 +/- 0.53 nmol/min/mg of microsomal protein. Other hydroxylated derivatives of eicosatetraenoic acid that possessed hydroxy groups at the 5- and 12-carbon atoms were not metabolized by the lung microsomes. This hydroxylation of 15-HETE was observed in lung microsomes of pregnant rabbits and only minor amounts were formed by nonpregnant rabbits. The specific activity for 15-HETE omega-hydroxylation was similar to the value obtained for prostaglandin E1 (1.48 +/- 0.33 nmol/min/mg). It is known that rabbit lungs possess a cytochrome P-450 that is induced during pregnancy and catalyzes the 20-hydroxylation of prostaglandins. The addition of the antibody to cytochrome P-450 prostaglandin omega-hydroxylase or prostaglandin E1, a substrate of this enzyme, resulted in potent inhibition of 15-HETE omega-hydroxylation, providing strong evidence that a common cytochrome P-450 catalyzes the omega-hydroxylation of both prostaglandins and 15-HETE.
Okita
R T
RT
Department of Biochemistry, Medical College of Wisconsin, Milwaukee 53226.
Soberman
R J
RJ
Bergholte
J M
JM
Masters
B S
BS
Hayes
R
R
Murphy
R C
RC
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D006900:Hydroxylation; D008168:Lung / Q000378:metabolism*; D013058:Mass Spectrometry; D008861:Microsomes / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011817:Rabbits
D006893:Hydroxyeicosatetraenoic Acids; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid