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- Title
Direct binding of ligandin to uridine 5'-diphosphate glucuronosyltransferase 1A1.
- Authors
Akizawa, Emi; Koiwai, Kotaro; Hayano, Takahide; Maezawa, So; Matsushita, Toyofumi; Koiwai, Osamu
- Abstract
Aim: Bilirubin, a final degradation product of heme produced mainly in the spleen, is carried to the liver through its binding to albumin in the blood circulation. After its transport to hepatocytes, ligandin (glutathione S-transferase; GST) carries bilirubin to the endoplasmic reticulum (ER). uridine 5'-diphosphate-glucuronosyltransferase 1A1 (UGT1A1) glucuronidates bilirubin for solubilization in the ER. Methods: By GST pull-down and co-immunoprecipitation assays, GSTA2, a member of the α-class of GST, was observed to directly bind to UGT1A1 through the region present inside the ER. Results: GSTA2 was detected in the microsomal fraction together with the cytosolic fraction after hepatocyte fractionation. Conclusion: These results strongly suggest that bilirubin is directly delivered to UGT1A1 from ligandin for glucuronidation.
- Subjects
URIDINE; AZARIBINE; PYROPHOSPHATES; GLUCURONOSYLTRANSFERASE; GLYCOSYLTRANSFERASES
- Publication
Hepatology Research, 2008, Vol 38, Issue 4, p402
- ISSN
1386-6346
- Publication type
Article
- DOI
10.1111/j.1872-034X.2007.00285.x