Differential effects of phospholipids on two similar forms of UDP-glucuronyltransferase purified from rat liver and kidney microsomes

Two isoforms of UDP-glucuronyltransferase purified from rat liver (named GT-1) and kidney (named GT-2) have various properties in common but differ in their NH2-terminal sequences. In this study, the two forms were further found to have common immunochemical properties, i.e., they could not be distinguished by Ouchterlony double diffusion and immunoblotting analyses. These isoforms also had the same inducibility as shown by immunoblotting analysis: GT-2 protein in rat was increased by treatment with beta-naphthoflavone and 3-methylcholanthrene, whereas GT-1 was inducible by 3-methylcholanthrene. However, the effects of phospholipids on these enzymes were extremely different. 1-Naphthol glucuronizing activity of GT-1 was increased 7.5-8-fold by lysophosphatidylcholine, but the activity of GT-2 was increased only 3-3.6-fold. The transferase activity of GT-1 toward 4-methylumbelliferone was increased 2-2.5-fold by dilauroylphosphatidylcholine, but that of GT-2 was reduced, while its 4-nitrophenol glucuronidation activity was increased 1.5-fold by the phospholipid. These results indicate that the two similar UDP-glucuronyltransferases from rat liver and kidney interact differently with phospholipids and that the activation level of UDP-glucuronyltransferase activity with phospholipids depends on the aglycone substrates.