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Drug Metab Rev. 2010 Feb;42(1):145-58. doi: 10.3109/03602530903208579.

Modulation of UDP-glucuronosyltransferase activity by protein-protein association.

Author information

  • 1Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. ishii@phar.kyushu-u.ac.jp

Abstract

Drug oxidation and conjugation mediated by cytochrome P450 (P450) and UDP-glucuronosyltransferase (UGT) have long been considered to take place separately. However, our recent studies have suggested that CYP3A4 specifically associates with UGT2B7 and alters the regioselectivity of morphine glucuronidation. This observation strongly supports the view that there is functional cooperation between P450 and UGT to facilitate multistep drug metabolism. In recent years, accumulating evidence has suggested an interaction between UGT isoforms or between P450 and UGTs and a change in UGT function by protein-protein association. In this review, we summarize these interactions and discuss their relevance to UGT function.

PMID:
19817679
[PubMed - indexed for MEDLINE]
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