Co-oxidation of xenobiotics.

Co-oxidation of xenobiotics has been shown t o occur during prostaglandin synthase (PGS)-catalysed synthesis of prostaglandins (Marnett. 198 I ; EIing et al.. 1983; Marnett & Eling. 1983). PGS catalyses the oxygenation of polyunsaturated fatty acids to hydroxy endoperoxides (e.g. PGH2). The most important substrate in vivo is arachidonic acid (AA) . PGS contains two activities: the fatty acid cyclooxygenase activity. which catalyses the oxygenation of AA t o a hydroperoxy endoperoxide (PGG2), and the hydroperoxidase activity, which catalyses the reduction of PGGz to the hydroxy endoperoxide (PGH2). PGH2 represents a branching point in the metabolism of AA and may then be further metabolized by other enzymes to various prostaglandins, throniboxanes and prostacyclins (Samuelsson et al.. 1978). PGS is associated with the endoplasmic reticulum and nuclear membranes, and is thus present in microsomal preparations. The cyclo-oxygenase activity of PGS is inhibited by non-steroidal anti-inflammatory agents such as