Comparison of Serotonin Glucuronidation Activity of UDP-glucuronosyltransferase 1a6a (Ugt1a6a) and Ugt1a6b: Evidence for the Preferential Expression of Ugt1a6a in the Mouse Brain

Mouse UDP-glucuronosyltransferase (Ugt) 1a6a and Ugt1a6b share 98% sequence homology, but there have been no reports to date that compare their expression levels or enzymatic activities in serotonin glucuronidation. Thus, we designed specific primers for Ugt1a6a and Ugt1a6b to compare their expression in mouse brain regions and livers. Ugt1a6a was dominantly expressed in mouse brains, especially the hippocampus, while both Ugt1a6a and Ugt1a6b were highly expressed in mouse livers, indicating that there are significant differences in the expression patterns of Ugt1a6a and Ugt1a6b among mouse tissues. Glucuronidation of endogenous neurotransmitter serotonin was catalyzed by Ugt1a6b with k(cat)/K-m (4.5 M-1.s(-1)) slightly higher than that of Ugt1a6a (2.4 M-1.s(-1)). However, the difference in expression levels between Ugt1a6a and Ugt1a6b in the hippocampus led us to speculate that Ugt1a6a is likely the predominant catalyst of serotonin glucuronidation in the mouse brain. In conclusion, we successfully elucidated the differences between Ugt1a6a and Ugt1a6b expression in the mouse brain. Our new findings indicate that Ugt1a6a and Ugt1a6b play different roles in mice, driven by differences in expression and kinetic properties for serotonin glucuronidation.