ArticleMolecular pharmacology2008
Novel polymorphic human UDP-glucuronosyltransferase 2A3: cloning, functional characterization of enzyme variants, comparative tissue expression, and gene induction.
Article in Molecular pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 63 citations in OpenAlex.
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- Analysis of in vitro and in vivo metabolism of zidovudine and gemfibrozil in trans-chromosomic mouse line expressing human UGT2 enzymes.Pharmacology research & perspectives · 2022Article
- Transcriptomic profiling of hepatic tissues for drug metabolism genes in nonalcoholic fatty liver disease: A study of human and animals.Frontiers in endocrinology · 2022Article
- Urinary Elimination of Bile Acid Glucuronides under Severe Cholestatic Situations: Contribution of Hepatic and Renal Glucuronidation Reactions.Canadian journal of gastroenterology & hepatology · 2018Article
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- Transcriptome analysis in primary colorectal cancer tissues from patients with and without liver metastases using next-generation sequencing.Cancer medicine · 2017Article
- Transcriptome association analysis identifies miR-375 as a major determinant of variable acetaminophen glucuronidation by human liver.Biochemical pharmacology · 2016Article
- Global liver gene expression differences in Nelore steers with divergent residual feed intake phenotypes.BMC genomics · 2015Article
- Renal drug metabolism in humans: the potential for drug-endobiotic interactions involving cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT).British journal of clinical pharmacology · 2013Review
- The Human UDP-glucuronosyltransferase UGT2A1 and UGT2A2 enzymes are highly active in bile acid glucuronidation.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Importance of UDP-glucuronosyltransferases 2A2 and 2A3 in tobacco carcinogen metabolism.Drug metabolism and disposition: the biological fate of chemicals · 2013Article
- Identification and functional characterization of a novel UDP-glucuronosyltransferase 2A1 splice variant: potential importance in tobacco-related cancer susceptibility.The Journal of pharmacology and experimental therapeutics · 2012Article
- Genetic variants in MicroRNA biosynthesis pathways and binding sites modify ovarian cancer risk, survival, and treatment response.Cancer research · 2010Article
- Alterations in hepatic mRNA expression of phase II enzymes and xenobiotic transporters after targeted disruption of hepatocyte nuclear factor 4 alpha.Toxicological sciences : an official journal of the Society of Toxicology · 2010Article
- Interindividual variability in hepatic drug glucuronidation: studies into the role of age, sex, enzyme inducers, and genetic polymorphism using the human liver bank as a model system.Drug metabolism reviews · 2010Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
UDP-glucuronosyltransferases (UGTs) are critical to the detoxification of numerous drugs, environmental pollutants, and endogenous molecules. However, as yet not all of the human UGTs have been cloned and characterized. cDNA clones from the UGT2A3 gene (located on chromosome 4q13) were isolated using pooled human liver RNA. Approximately 10% of clones contained a c.1489A>G nucleotide substitution, yielding proteins with a residue 497 alanine (UGT2A3.2) instead of a threonine (UGT2A3.1). The allele frequency of this polymorphism (rs13128286) was 0.13 in a European-American population as determined by direct DNA sequencing. Of 81 structurally diverse glucuronidation substrates tested, UGT2A3 expressed by a baculovirus system selectively glucuronidated bile acids, particularly hyodeoxycholic acid at the 6-hydroxy position. Apparent K(m) values of UGT2A3.1 and UGT2A3.2 for hyodeoxycholic acid 6-glucuronidation were 69 +/- 7 and 44 +/- 12 microM, respectively. Of 29 different extrahepatic tissues evaluated by real-time polymerase chain reaction, UGT2A3 mRNA was most highly expressed in small intestine (160% of liver), colon (78% of liver), and adipose tissue (91% of liver). An in silico scan of the proximal UGT2A3 promoter/5'-regulatory region identified transcription factor consensus elements consistent with tissue-selective expression in liver (HNF1) and intestine (CXD2), as well as induction by rifampicin (pregnane X receptor). In LS180 human intestinal cells, rifampicin increased UGT2A3 mRNA by more than 4.5-fold compared with vehicle, whereas levels were not significantly affected by the arylhydrocarbon receptor ligand beta-naphthoflavone. This is the first report establishing UGT2A3 as a functional enzyme, and it represents significant progress toward the goal of having a complete set of recombinant human UGTs for comparative functional analyses.
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