I. Evidence for Separate Enzymes in the Glucuronidation of Morphine and p-Nitrophenol by Rat Hepatic Microsomes
Abstract
Morphine glucuronide and p-nitrophenyl glucuronide synthesis have been measured in rat hepatic microsomes or detergent-activated microsomal preparations. The effect of alternate substrate interaction and induction of the UDP-glucuronyltransferase activity for each substrate has been determined. In the presence of excess UDP-glucuronic acid, morphine and p-nitrophenol were not mutually inhibitory. p-Nitrophenyl glucuronide competitively inhibited p-nitrophenol glucuronidation but had no effect on morphine glucuronidation in rat hepatic microsomes. Differential rates of enhancement in the glucuronidation of morphine and p-nitrophenol were observed in hepatic microsomal preparations from rats chronically treated with phenobarbital or 3-methylcholanthrene. Rates of p-nitrophenol glucuronidation were lower in hepatic microsomes from adult rats than hepatic microsomes from newborn rats, whereas morphine glucuronidation was similar in these preparations. Results suggest that separate UDP-glucuronyltransferases (EC 2.4.1.17) catalyze the glucuronidation of morphine and p-nitrophenol in rat hepatic microsomes.
Footnotes
- Received January 3, 1974.
- Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics
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