Metabolism of naphthalene to naphthalene dihydrodiol glucuronide in isolated hepatocytes and in liver microsomes

The functional linkage between UDP-glucuronyltransferase (GT) and the monooxygenase-epoxide hydratase system was investigated in studies on the glucuronidation of naphthalene dihydrodiol, which was formed by epoxide hydratase during the metabolism of naphthalene. (1) Naphthalene metabolism was compared in isolated hepatocytes and in liver microsomes incubated with an NADPH regenerating system and UDP-glucuronic acid. Naphthalene dihydrodiol glucuronide was a major metabolite in isolated hepatocytes. In the liver microsomal system free dihydrodiol by far exceeded its glucuronide unless the positive allosteric effector of GT, UDP-N-acetylglucosamine, was added. (2) Treatment of rats with phenobarbital or 3-methylcholanthrene, although markedly enhancing the formation of naphthalene dihydrodiol, did not stimulate liver microsomal GT (naphthalene dihydrodiol as substrate). The results suggest that activation of GT by UDP-N-acetylglucosamine is an important factor in the coupling of glucuronidation to functionally linked microsomal enzyme reactions.