RGD Reference Report - UDP-glucuronosyltransferase isoforms catalyzing glucuronidation of hydroxy-polychlorinated biphenyls in rat. - Rat Genome Database

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UDP-glucuronosyltransferase isoforms catalyzing glucuronidation of hydroxy-polychlorinated biphenyls in rat.

Authors: Daidoji, T  Gozu, K  Iwano, H  Inoue, H  Yokota, H 
Citation: Daidoji T, etal., Drug Metab Dispos. 2005 Oct;33(10):1466-76. Epub 2005 Jul 8.
RGD ID: 1600442
Pubmed: PMID:16006569   (View Abstract at PubMed)
DOI: DOI:10.1124/dmd.105.004416   (Journal Full-text)

Polychlorinated biphenyls (PCBs) are highly toxic environmental contaminants that can cause irreversible damage in humans and wildlife. The mechanism of toxicity is not clear, but biotransformation products such as hydroxy PCBs (OH-PCBs) are a major concern. Efforts to elucidate the metabolism of PCBs and their metabolites, however, have paid little attention to the structure of the compound to be eliminated. The objectives of this study were to clarify organ tissue distribution of the glucuronidation activities toward OH-PCBs and to determine the UDP-glucuronosyltranseferase (UGT) isoforms responsible for glucuronidation in relation to the OH-PCB structure. 2,4,6-Trichlorobiphenyl and 2,3,4,5-tetrachlorobiphenyl were incubated in primary culture of rat hepatocytes, and the metabolites were identified by HPLC. Organ tissue glucuronidation activities toward 10 OH-PCBs were investigated by reactions of microsomes prepared from brain, liver, small and large intestine, lung, kidney, and testis tissues. To determine substrate specificity of the isoforms toward the OH-PCBs, rat UGT isoforms UGT1A1, UGT1A3, UGT1A5, UGT1A6, UGT1A7, UGT2B1, UGT2B3, and UGT2B12 were expressed in yeast strain AH22. Glucuronidation of the PCBs was found to be contingent on their hydroxylation. The organ tissues had strong glucuronidation activities toward the OH-PCBs tested; and most OH-PCBs were glucuronidated by UGT1A1, UGT1A6, and UGT2B1, all of which were substrate-specific. In conclusion, glucuronidation activities of UGT1A1, UGT1A6, and UGT2B1 toward OH-PCBs is relative to expression of the isoforms in each tissue, and glucuronidation intensity of the isoforms is relative to the structure of the OH-PCB to be glucuronidated.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
4-chlorobiphenyl metabolic process  IDA 1600442 RGD 
biphenyl catabolic process  IDA 1600442; 1600442 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glucuronosyltransferase activity  IDA 1600442 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ugt1a1  (UDP glucuronosyltransferase family 1 member A1)
Ugt1a6  (UDP glucuronosyltransferase family 1 member A6)
Ugt2b1  (UDP glucuronosyltransferase 2 family, polypeptide B1)

Objects referenced in this article
Gene Ube2b ubiquitin-conjugating enzyme E2B Rattus norvegicus

Additional Information