Disease relevance of UGT2B11

• In liver microsomes from four patients (A, B, C, and D) with Crigler-Najjar syndrome type I (CN type I), UDPGT activity towards bilirubin was undetectable (A, B, C, and D) and activity towards phenolic compounds and 5-hydroxytryptamine either reduced (A and B) or normal (C and D) [1].
• Concurrent with this decrease in T4 was an increase in TSH levels, an increase in thyroid and liver weights, a three- to sixfold increase in hepatic T4-uridine diphosphate glucuronosyl transferase (UDPGT) activity, and increases in thyroid follicular cell hypertrophy and hyperplasia [2].

High impact information on UGT2B11

• These findings suggest considerable heterogeneity with regard to the expression of UDPGT isoenzymes among CN type I patients [1].
• Biochanin A significantly decreased the testosterone-stimulated release of PSA, presumably because biochanin A increased UDPGT and increased the intracellular glucuronidation of testosterone [3].
• The steroid form of the UDPGT transcript was expressed in LNCaP cells and was enhanced in biochanin A-treated LNCaP cells [3].
• 1. The other PAC clones isolated contain exons from the UGT2B4, UGT2B11 and UGT2B17 genes [4].
• In human prostate epithelial cells, only UGT2B11 and -B15 mRNAs are detected and are regulated by androgens in a similar manner as in LNCaP cells [5].

Chemical compound and disease context of UGT2B11

• Crigler-Najjar syndrome type 1 (CN type 1) is an autosomal recessive disorder characterized by nonhemolytic jaundice resulting from mutations to the gene encoding bilirubin-UDP-glucuronosyltransferase (UDPGT) [6].

Biological context of UGT2B11

• The glucuronidation of 3'-azido-3'-deoxythymidine (AZT) by human liver microsomes and human hepatocytes in culture has been studied in vitro to determine the UDP-glucuronosyltransferase (UDPGT) form conceivably involved in the AZT biotransformation process [7].
• The differential expression of UDPGT in the four tissues clearly demonstrated for the first time that multiple isoforms with differing substrate specificities were present in fish [8].
• In comparison with the amino acid sequences of seven species of glucosyltransferases and six species of galactosyltransferases, glutamine and histidine are highly conserved as the last amino acid residue of a glycosyltransferase-specific conserved region (UDPGT) in glucosyltransferases and galactosyltransferases, respectively [9].
• In embryonic and early fetal development of the metanephric kidney, UDPGT is located primarily in derivatives of the ureteric bud such as the ureter, pelvis, calyces and collecting ducts [10].

Anatomical context of UGT2B11

• The significance of a possible induction of UDPGT in human foetal liver cells by HgCl2 is discussed [11].
• Increased thyroid T4 elimination, primarily via increased hepatic conjugation by T4-UDPGT, resulting in decreased serum T4, appeared to be responsible for the increased TSH levels [2].
• The results indicate that the 55-kDa polypeptide was the major polyaromatic hydrocarbon-inducible UDPGT isoenzyme in hepatic and renal microsomes [8].

Associations of UGT2B11 with chemical compounds

• Using a cell-free assay with testosterone as substrate, we showed that LNCaP had UDP-glucuronosyltransferase (UDPGT) activity [3].
• Kinetic studies of the glucuronidation reaction with harmol and 1-naphthol showed that Hg2+ ions seemed to induce the expression of a high-affinity form of UDPGT, which was absent from the normal controls [11].
• The dramatic increase in specific activity in UDPGT was accompanied by a parallel increase in Vmax. measured with harmol and UDP-glucuronic acid [11].
• The enzymatic glucuronidation of 3'-azido-3'-deoxythymidine (AZT) catalyzed by human liver microsomal UDP-glucuronosyltransferase (EC 2.4.1.17, UDPGT) was inhibited by a number of nucleoside analogs [12].
• Three homologous inhibitors, 3'-azido-2',3'-dideoxyuridine (AzddU), 5-ethyl-AzddU, and 5-propyl-AzddU, were also studied as substrates of UDPGT [12].

Analytical, diagnostic and therapeutic context of UGT2B11

• To investigate this possibility directly, UDPGT was extracted from human liver and kidney tissue and its activity was characterized using MPA as a substrate in vitro, assessing the conversion of MPA to MPAG using analysis by high-performance liquid chromatography [13].
• With further UDPGT purification (approximately 200-fold) from kidney extracts using a combination of ammonium sulfate precipitation, followed by anion exchange, hydroxyapatite, and size exclusion chromatography, the enzyme was more than 80% pure when assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis [13].

References