Presystemic glucuronidation of morphine in humans and rhesus monkeys: subcellular distribution of the UDP-glucuronyltransferase in the liver and intestine

Abstract

1. Glucuronyltransferase (GT) activity was measured in the homogenate and in the nuclear, mitochondrial and microsomal fractions of liver and intestinal mucosa from man and rats. 2. In man the average rate of morphine glucuronidation was 0.58 and 0.27 nmol/min per mg protein in the homogenates of the liver and intestinal mucosa, respectively. 3. GT was evenly distributed in the different fractions of liver, whereas the major part of the activity in the intestinal mucosa was associated with the nuclear fraction. There was a larger difference between the GT activities in the microsomal fractions of the liver and intestine (0.68 and 0.06 nmol/min per mg, respectively), than between the homogenates of these organs. 4. Similar results were obtained in the rat. GT activity in homogenates of the liver and intestine differed only three-fold whereas there was an 18-fold difference between the microsomal GT activities in these organs.