The influence of the 3-hydroxyl and N-alkyl groups in the reactivity of narcotic compounds with morphine UDP-glucuronyltransferase was studied. Opioids possessing both, one or none of these groups were tested for inhibition of morphine glucuronidation in rabbit liver microsomal preparations. Compounds with only a 3-hydroxyl group (normorphine) or an N-methyl group (codeine, ethylmorphine) were less potent competitive inhibitors than those containing both groups (dextrorphan). Norcodeine, with neither of these groups, had no inhibitory effect. The synthetic narcotics (+)- and (-)-methadone, (-)-alpha-acetylmethadol and meperidine, with only an N-alkyl group, were effective competitive inhibitors. No stereoselectivity of the morphine glucuronyltransferase for opioid isomers was observed, and [methionine]enkephalin does not react with morphine glucuronyltransferase. Differences of pKa values and water/lipid solubility of narcotics could not explain the effects. Results indicate that the N-alkyl group plays a critical role in the interaction of narcotics with the morphine UDP-glucuronyltransferase.
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January 1978
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Research Article|
January 01 1978
Structural requirements in the reaction of morphine uridine diphosphate glucuronyltransferase with opioid substances
Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1978 London: The Biochemical Society
1978
Biochem J (1978) 169 (1): 173–177.
Citation
E Sanchez, E Del Villar, T R Tephly; Structural requirements in the reaction of morphine uridine diphosphate glucuronyltransferase with opioid substances. Biochem J 1 January 1978; 169 (1): 173–177. doi: https://doi.org/10.1042/bj1690173
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