Metabolism of linoleic acid by prostaglandin endoperoxide synthase from adult and fetal blood vessels

Abstract

Linoleic acid (18:2) is converted by prostaglandin endoperoxide synthase in paniculate fractions and homogenates of fetal calf aorta to its 9- and 13-hydroperoxy metabolites. These intermediates are then either dehydrated to the corresponding oxo compounds or reduced to monohydroxy products. Alternatively, the hydroperoxyoctadecadienoic acids can be converted to epoxyhydroxyoctadecenoic acids, which are hydrolyzed to trihydroxy metabolites by epoxide hydrolases present in both particulate and cytosolic fractions from aorta. Linoleic acid (Km, 442 μM) is a much poorer substrate for prostaglandin endoperoxide synthase than is arachidonic acid (20:4) (Km, 48 μM). However, the oxygenation of 18:2 by particulate fractions from aorta is linear with time for at least 5 min, whereas the oxygenation of 20:4 is linear for only 15 s. Arachidonic acid strongly inhibits the conversion of 18:2 to monohydroxy (ID50, 10 μM) and trihydroxy (ID50, 140 μM) products. Linoleic acid has a similar, but much weaker effect on the formation of 6-oxoprostaglandin F1 α from 20:4. Substantial amounts of both the monohydroxy (9-hydroxy-1O, 12-oc-tadecadienoic acid and 13-hydroxy-9, ll-octadecadienoic acid) and trihydroxy (9,10,ll-trihydroxy-12-oc-tadecenoic acid, 9,10,13-trihydroxy-ll-octadecenoic acid and 9,12,13-trihydroxy-lO-octadecenoic acid) metabolites of 18:2 were shown by gas chromatography-mass spectrometry to be formed from endogenous substrate during incubation of slices of fetal calf aorta in physiological medium. This raises the possibility that some of these products or their hydroperoxy precursors may have some biological significance.