UDP-glucuronyltransferase in perfused rat liver and in microsomes. Glucuronidation of bilirubin

Abstract

In perfused rat liver and in fistula rats the formation of bilirubin conjugates was studied after labeling with [14C]bilirubin,5-amino [14C]levulinic acid and [14C]hemin. The latter two compounds were used to study heme degradation to bilirubin from intrahepatic and extrahepatic sources, respectively. Bilirubin glucuronides were the major conjugates in fistula bile. In liver perfusion bile the proportion of non-glucuronide conjugates was increased. After a high dose of hemin (2.5 mumol) bilirubin glucuronides were decreased compared with other bilirubin conjugates both in fistula bile and in liver perfusion bile. In addition green pigments were formed. These alterations were reversed in chronically hemin-treated rats in which heme oxygenase had been induced. The interference of UDP-glucose and UDP-glucuronic acid with bilirubin glucuronidation and glucosidation was studied in liver microsomes. UDP-glucose did not affect bilirubin glucuronidation in native microsomes in which UDP-glucuronyltransferase activity is constrained. When this constraint was released by various treatments altering membrane structure UDP-glucose markedly inhibited bilirubin glucuronidation. However, under these conditions bilirubin glucosidation was unaffected by UDP-glucuronic acid. The results suggest that the release of the constraint of UDP-glucuronyltransferase in vivo may lead to a decrease of the proportion of bilirubin glucuronides to other bilirubin conjugates in bile.