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. 2008 Apr;38(4):402-9.
doi: 10.1111/j.1872-034X.2007.00285.x. Epub 2007 Nov 16.

Direct binding of ligandin to uridine 5'-diphosphate glucuronosyltransferase 1A1

Emi Akizawa  1 , Kotaro Koiwai, Takahide Hayano, So Maezawa, Toyofumi Matsushita, Osamu Koiwai
Affiliations

Direct binding of ligandin to uridine 5'-diphosphate glucuronosyltransferase 1A1

Emi Akizawa et al. Hepatol Res. 2008 Apr.

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 alpha-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.

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