Disease relevance of Ugt2b5

• Gunn rats are a mutant strain of Wistar rats that have unconjugated hyperbilirubinemia due to absence of hepatic uridine diphosphate-glucuronosyltransferase (UDPGT; EC. 2.4.1.17) activity toward bilirubin [1].
• The inbred homozygous Gunn rat is also deficient in UDPGT, exhibits unconjugated hyperbilirubinemia, and is an excellent animal model of the Crigler-Najjar syndrome [2].
• 4-CB might also alter the normal imprinting of sexual differentiation of hepatic metabolism as evidenced by a feminization (decrease) of UDPGT in adult male rats which were exposed neonatally to 4-CB [3].
• These results indicate that the effect of SF is similar to those of PB and thyroid hypertrophy seen in the oral 2-week treatment with SF, and may be caused by indirectly elevated TSH levels which resulted from the induction of hepatic UDPGT activity [4].

High impact information on Ugt2b5

• UDPGT isoform I (elution pH 8.7) from Wistar (RHA) and Gunn rats was active toward 4-nitrophenol [1].
• Isoforms II (elution pH 8.4), III (elution pH 8.0), and IV (elution pH 7.8) from Gunn rats had normal UDPGT activities, except that Isoform IV was inactive toward bilirubin [1].
• The corresponding isoform from Gunn rat liver was enzymically inactive but exhibited normal elution pH and mobility on NaDodSO4/polyacrylamide gel electrophoresis (Mr 53,000), and was recognized by a UDPGT-specific antiserum [1].
• The isoform from Gunn rat liver had only 10% of normal UDPGT activity, however UDPGT activity increased to normal upon addition of 15 mM diethylnitrosamine in vitro [1].
• Of the purified enzymes investigated, only 3 alpha-hydroxysteroid UDPGT catalyzed the glucuronidation of 4-aminobiphenyl. alpha-Naphthylamine and beta-naphthylamine conjugations were catalyzed by 3 alpha-hydroxysteroid, 17 beta-hydroxysteroid, and 3-methylcholanthrene-inducible p-nitrophenol UDPGTs [5].

Biological context of Ugt2b5

• The 1871-base pair (bp) cDNA, designated UDPGTr-5, contains an open reading frame of 1590 bp flanked by 43 and 238 bp of 5'- and 3'-untranslated regions, respectively [6].
• These studies suggest that flunitrazepam binds rather selectively to the morphine binding site of morphine UDPGT and may prove to be a useful probe for this enzyme [7].
• T3 UDPGT activity showed a discontinuous variation, which completely matched the genetic heterogeneity in androsterone glucuronidation in Wistar rats [8].
• UDPGT activities tested could be divided in four groups on the basis of their tissue distribution and induction by PB or 3MC in liver microsomes [9].
• These observations suggest that UDP-glucuronosyltransferase (UDPGT), EC2.4.1.17, mediates the in vivo biotransformation of AZT to GAZT [10].

Anatomical context of Ugt2b5

• Expression of UDPGTr-5 cDNA in COS cells demonstrated that the encoded enzyme has a subunit size of 50 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis [6].
• Immunoblot analysis of microsomes from developing rat liver demonstrated that the deficiency in bilirubin and testosterone glucuronidation in the fetus was due to the absence of the UDPGT isoenzyme proteins responsible for these conjugations [11].
• Using an improved procedure to isolate pure bile ductular epithelial cells from rat liver, we were able to define UDP-glucuronosyl transferase (UDPGT) isozymes expressed in these cells under physiological conditions [12].
• CONCLUSION: Transplants of small intestine with known UDPGT activity partially corrected the deficiency in Gunn rats and allayed the hyperbilirubinemia [2].
• Steroid glucuronidation was investigated in solubilized female rat and rabbit liver microsomes and in preparations of UDP-glucuronsyltransferase (UDPGT) activity resolved from these organelles [13].

Associations of Ugt2b5 with chemical compounds

• Crabp2, Fabp1, and Ugt2b5 were differentially expressed between ACI and BUF rats both before and after MNNG treatment [14].
• UDPGT isoform V (elution pH 7.5) from Wistar (RHA) rats is active toward bilirubin and 4'-hydroxydimethylaminoazobenzene [1].
• Chromatofocusing chromatography showed that flunitrazepam bound only to fractions containing active morphine UDPGT, and no binding to 4-hydroxybiphenyl UDPGT was observed [7].
• Because flunitrazepam is an effective photoaffinity label for benzodiazepine receptors, studied were performed in solubilized rat hepatic microsomes and with partially purified preparations of morphine UDPGT to determine the enhancement of flunitrazepam inhibition and binding to morphine UDPGT promoted by exposure to UV light [7].
• Parallel to the chemoprotection experiments, the modulation of the activities of cytochrome P4501A2, glutathione-S-transferase (GST) and UDP glucuronosyltransferase (UDPGT) by GC juice, GT and BITC was studied [15].

Other interactions of Ugt2b5

• Although Crabp2 had been identified as one of the 16 genes differentially expressed between ACI and BUF rats with cDNA-RDA, Fabp1 and Ugt2b5 were newly identified in this study [14].

Analytical, diagnostic and therapeutic context of Ugt2b5

• Sequence analysis of peptides obtained by CNBr cleavage of purified gp56 indicates that it is highly homologous to UDP-glucuronosyl transferase (UDPGT) [16].
• UDPGT activity was purified from rat kidney by a combination of ion-exchange chromatography, gel filtration and affinity chromatography on UDP-hexanolamine Sepharose [17].
• No induction of renal UDPGT was observed after phenobarbital treatment, but renal bilirubin UDPGT activity was specifically induced after treatment of rats with clofibrate [17].
• The UDPGT isoenzymes were purified utilizing Chromatofocusing, column isoelectric focusing, and UDP-hexanolamine Sepharose 4B affinity chromatography [18].
• The activity of hepatic glutathione S-transferase (GST) and UDP-glucuronyl transferase (UDPGT) and the level of glutathione (GSH) were estimated at 0, 45 and 90 days of treatment as well as 28 days after cessation of treatment [19].

References