Glucuronidation of Morphine in Human Kidney Microsomes

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Abstract
The UDP-glucuronyltransferase (GT) activity with morphine as substrate was measured in microsomes prepared from seven human adult kidneys including one whose cortex and medulla had been separated. The formation of morphine-3- and 6-glucuronides (M3G and M6G) was determined by HPLC methods. All kidney specimens formed M3G and M6G when incubated with morphine and UDP-glucuronic acid (UDPGA). The estimated Vmax and Km of morphine to form M3G and M6G were 2.2 and 0.18 nmol per mg protein and min. and 8.2 and 4.6 mM, respectively. The corresponding values for UDPGA were 1.3 and 0.13 nmol per mg protein and min. and 5.4 and 4.1 mM, respectively. The GT activity in cortex was 2.8-fold higher than in the medulla. The human kidney thus contains glucuronyltransferase activities towards morphine, which is in contrast to previous findings in the rat.