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UGT2B10
UGT2B10 Full Name
UDP glucuronosyltransferase 2 family, polypeptide B10
UGT2B10 Introduction
UGT2B10 encodes a UDP-glucuronosyltransferase within the UGT2B subfamily, a distinct branch of the human glucuronidation enzyme network that also includes the related UGT2B7 and UGT2B15 isoforms. As with other UGTs, UGT2B10 catalyzes the transfer of glucuronic acid from UDP-glucuronic acid to acceptor molecules, increasing their water solubility and promoting excretion. UGT2B10 is expressed in several tissues, including the liver and respiratory tract, and its localization in smoking-exposed organs has drawn particular interest. The enzyme contributes to the phase II metabolism of both endogenous compounds and foreign chemicals, and it is best characterized for its role in processing nicotine and its primary metabolite cotinine. Members of the UGT2B subfamily are distinguished from the UGT1A enzymes by their genomic organization and by overlapping but non-identical substrate preferences, and UGT2B10 occupies a specialized niche focused on small alkaloids and related compounds.
Figure 1. Major pathways of nicotine metabolism. (Source: Sipe CJ, et al. 2020)
UGT2B10 is a major enzyme responsible for the glucuronidation of nicotine and cotinine, reactions that determine how the body clears tobacco-derived compounds. A well-studied missense variant, D67Y, dramatically reduces or abolishes enzyme activity and is found at appreciable frequency in populations of African ancestry, leading to substantially different nicotine clearance between individuals. Investigations across ethnic groups have revealed extensive haplotype diversity and copy-number variation at the UGT2B locus, which helps explain interindividual and interpopulation differences in smoking-related metabolism. The enzyme's activity is also subject to developmental and tissue-specific regulation, so its contribution to clearance can differ across organs and life stages. Because nicotine glucuronidation influences both the elimination of tobacco alkaloids and the formation of metabolites associated with tobacco-related carcinogen exposure, UGT2B10 variation has implications for smoking behavior, dependence, and cancer risk. Together with its sibling isoforms, UGT2B10 illustrates how genetic diversity in conjugation enzymes shapes personal differences in xenobiotic handling.
Alternate Names for UGT2B10
UGT2B10; UDP glucuronosyltransferase 2 family, polypeptide B10; UDP glycosyltransferase 2 family, polypeptide B10; UDP-glucuronosyltransferase 2B10; UDPGT 2B10; UDP glucuronosyltransferase 2B10; UDPGT2B10; MGC142209;
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