alexa First-pass metabolism via UDP-glucuronosyltransferase: a barrier to oral bioavailability of phenolics.
Molecular Biology

Molecular Biology

Journal of Cytology & Histology

Author(s): Wu B, Kulkarni K, Basu S, Zhang S, Hu M

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Abstract Glucuronidation mediated by UDP-glucuronosyltransferases (UGTs) is a significant metabolic pathway that facilitates efficient elimination of numerous endobiotics and xenobiotics, including phenolics. UGT genetic deficiency and polymorphisms or inhibition of glucuronidation by concomitant use of drugs are associated with inherited physiological disorders or drug-induced toxicities. Moreover, extensive glucuronidation can be a barrier to oral bioavailability as the first-pass glucuronidation (or premature clearance by UGTs) of orally administered agents usually results in the poor oral bioavailability and lack of efficacies. This review focused on the first-pass glucuronidation of phenolics including natural polyphenols and pharmaceuticals. The complexity of UGT-mediated metabolism of phenolics is highlighted with species-, gender-, organ- and isoform-dependent specificity, as well as functional compensation between UGT1A and 2B subfamily. In addition, recent advances are discussed with respect to the mechanisms of enzymatic actions, including the important properties such as binding pocket size and phosphorylation requirements. Copyright © 2011 Wiley-Liss, Inc.
This article was published in J Pharm Sci and referenced in Journal of Cytology & Histology

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