Metabolism of eicosapentaenoic acid by aorta: formation of a novel 13-hydroxylated prostaglandin.
We have investigated the metabolism by fetal calf aorta of eicosapentaenoic acid (20:5) and docosahexaenoic acid (22:6), two polyunsaturated fatty acids found in high concentrations in marine oils. The major product formed from 20:5 by particulate fractions from fetal calf aorta is delta 17-6-oxoprostaglandin F1 alpha. In addition, we detected a novel isomer of delta 17-6-oxoprostaglandin F1 alpha, in which a hydroxyl group is present in the 13-position instead of the 15-position. Eicosapentaenoic acid is also converted to 12-hydroxy-5,8,10,14-heptadecatetraenoic acid as well as to five monohydroxy isomers with hydroxyl groups present in the 11, 12, 14, 15, and 18 positions. Although 20:5 was metabolized at about one-third the rate of arachidonic acid (20:4), greater amounts of monohydroxy fatty acids, the major one being the 11-hydroxy metabolite, were formed from 20:5. Unlike 20:5, 22:6 was not metabolized to any detectable products by fetal calf aorta, but both of these polyunsaturated fatty acids inhibited the oxygenation of 20:4 by cyclooxygenase from aorta with IC50 values of 4.1 microM (22:6) and 15 microM (20:5). These results suggest that 20:5 has a high affinity for cyclooxygenase, but that the intermediate 11-oxygenated intermediate has a lower affinity than the corresponding intermediate from 20:4, resulting in a greater loss of substrate after a single oxygenation. The formation of oxygenation products from both 20:4 and 20:5 was inhibited by 13-hydroperoxy-9,11-octadecadienoic acid (13hp-18:2). The IC50 values for inhibition of cyclooxygenase products by 13hp-18:2 were about twice as high as those for inhibition of prostacyclin synthase products. Consequently, there was little diversion of prostaglandin endoperoxides to other prostaglandins in the presence of 13hp-18:2.
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D000818:Animals; D001011:Aorta / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D015118:Eicosapentaenoic Acid; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D005333:Fetus; D008401:Gas Chromatography-Mass Spectrometry; D007700:Kinetics; D008041:Linoleic Acids / Q000096:biosynthesis*; D008054:Lipid Peroxides; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis* / Q000302:isolation & purification
D002250:Carbon Radioisotopes; D005231:Fatty Acids, Unsaturated; D008041:Linoleic Acids; D008054:Lipid Peroxides; D011453:Prostaglandins; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D015118:Eicosapentaenoic Acid; D011451:Prostaglandin-Endoperoxide Synthases