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YANNICK GOUMON Y COLS. AN. R. ACAD. NAC. FARM.
endogenous and exogenous morphine could be glucuronized inside
this organ (34, 35).
These various forms of UGT have distinct but overlapping
substrate specificities. To date, 28 different UGT genes have been
identified and these have been divided into two families and sub-
families (UGT1, UGT2A and UGT2B) on the basis of their homology
(36). Only certain of the known human UGTs appear to be catalytically
active, namely UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9, 1A10, 2A1,
2B4, 2B7, 2B15, 2B17 and 2B28 (37, 38). In the liver, morphine
is glucuronidated by a UGT at Carbon 3 or 6, to generate either
morphine-3-glucuronide (M3G) or morphine-6-glucuronide (M6G;
Figure 1), both highly hydrophilic compounds which are quickly
excreted in the urine.
Figure 1. UGT2B7-catalysed generation of M3G and M6G from morphine in the
liver.
M3G accounts for about 90% of the glucuronide products and has
no analgesic activity at all (Figure 1). In contrast, M6G (the other 10%
of morphine glucuronide products in the liver) is reported to be a
more potent analgesic than the parent molecule [reviewed in: (32)].
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