Modulation of UDP-glucuronosyltransferase activity by endogenous compounds

Yuji Ishii, Arief Nurrochmad, Hideyuki Yamada

Research output: Contribution to journalReview article

23 Citations (Scopus)

Abstract

Glucuronidation is one of the major pathways of metabolism of endo- and xenobiotics. UDP-Glucuronosyltransferase (UGT)-catalyzed glucuronidation accounts for up to 35z of phase II reactions. The expression and function of UGT is modulated by gene regulation, post-translational modifications and protein-protein association. Many studies have focused on drug-drug interactions involving UGT, and there are a number of reports describing the inhibition of UGT by xenobiotics. However, studies about the role of endogenous compounds as an inhibitor or activator of UGT are limited, and it is important to understand any change in the function and regulation of UGT by endogenous compounds. Recent studies in our laboratory have shown that fatty acyl-CoAs are endogenous activators of UGT, although fatty acyl-CoAs had been considered as inhibitors of UGT. Further, we have also suggested that adenine and related compounds are endogenous allosteric inhibitors of UGT. In this review, we summarize the endogenous modulators of UGT and discuss their relevance to UGT function.

Original languageEnglish
Pages (from-to)134-148
Number of pages15
JournalDrug metabolism and pharmacokinetics
Volume25
Issue number2
DOIs
Publication statusPublished - Jan 1 2010

Fingerprint

Glucuronosyltransferase
Xenobiotics
Adenine
Post Translational Protein Processing
Drug Interactions

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

Cite this

Modulation of UDP-glucuronosyltransferase activity by endogenous compounds. / Ishii, Yuji; Nurrochmad, Arief; Yamada, Hideyuki.

In: Drug metabolism and pharmacokinetics, Vol. 25, No. 2, 01.01.2010, p. 134-148.

Research output: Contribution to journalReview article

Ishii, Yuji ; Nurrochmad, Arief ; Yamada, Hideyuki. / Modulation of UDP-glucuronosyltransferase activity by endogenous compounds. In: Drug metabolism and pharmacokinetics. 2010 ; Vol. 25, No. 2. pp. 134-148.
@article{c47dd8e7d57344eaa85917e8fc92d551,
title = "Modulation of UDP-glucuronosyltransferase activity by endogenous compounds",
abstract = "Glucuronidation is one of the major pathways of metabolism of endo- and xenobiotics. UDP-Glucuronosyltransferase (UGT)-catalyzed glucuronidation accounts for up to 35z of phase II reactions. The expression and function of UGT is modulated by gene regulation, post-translational modifications and protein-protein association. Many studies have focused on drug-drug interactions involving UGT, and there are a number of reports describing the inhibition of UGT by xenobiotics. However, studies about the role of endogenous compounds as an inhibitor or activator of UGT are limited, and it is important to understand any change in the function and regulation of UGT by endogenous compounds. Recent studies in our laboratory have shown that fatty acyl-CoAs are endogenous activators of UGT, although fatty acyl-CoAs had been considered as inhibitors of UGT. Further, we have also suggested that adenine and related compounds are endogenous allosteric inhibitors of UGT. In this review, we summarize the endogenous modulators of UGT and discuss their relevance to UGT function.",
author = "Yuji Ishii and Arief Nurrochmad and Hideyuki Yamada",
year = "2010",
month = "1",
day = "1",
doi = "10.2133/dmpk.25.134",
language = "English",
volume = "25",
pages = "134--148",
journal = "Drug Metabolism and Pharmacokinetics",
issn = "1347-4367",
publisher = "Japanese Society for the Study of Xenobiotics",
number = "2",

}

TY - JOUR

T1 - Modulation of UDP-glucuronosyltransferase activity by endogenous compounds

AU - Ishii, Yuji

AU - Nurrochmad, Arief

AU - Yamada, Hideyuki

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Glucuronidation is one of the major pathways of metabolism of endo- and xenobiotics. UDP-Glucuronosyltransferase (UGT)-catalyzed glucuronidation accounts for up to 35z of phase II reactions. The expression and function of UGT is modulated by gene regulation, post-translational modifications and protein-protein association. Many studies have focused on drug-drug interactions involving UGT, and there are a number of reports describing the inhibition of UGT by xenobiotics. However, studies about the role of endogenous compounds as an inhibitor or activator of UGT are limited, and it is important to understand any change in the function and regulation of UGT by endogenous compounds. Recent studies in our laboratory have shown that fatty acyl-CoAs are endogenous activators of UGT, although fatty acyl-CoAs had been considered as inhibitors of UGT. Further, we have also suggested that adenine and related compounds are endogenous allosteric inhibitors of UGT. In this review, we summarize the endogenous modulators of UGT and discuss their relevance to UGT function.

AB - Glucuronidation is one of the major pathways of metabolism of endo- and xenobiotics. UDP-Glucuronosyltransferase (UGT)-catalyzed glucuronidation accounts for up to 35z of phase II reactions. The expression and function of UGT is modulated by gene regulation, post-translational modifications and protein-protein association. Many studies have focused on drug-drug interactions involving UGT, and there are a number of reports describing the inhibition of UGT by xenobiotics. However, studies about the role of endogenous compounds as an inhibitor or activator of UGT are limited, and it is important to understand any change in the function and regulation of UGT by endogenous compounds. Recent studies in our laboratory have shown that fatty acyl-CoAs are endogenous activators of UGT, although fatty acyl-CoAs had been considered as inhibitors of UGT. Further, we have also suggested that adenine and related compounds are endogenous allosteric inhibitors of UGT. In this review, we summarize the endogenous modulators of UGT and discuss their relevance to UGT function.

UR - http://www.scopus.com/inward/record.url?scp=77952662988&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952662988&partnerID=8YFLogxK

U2 - 10.2133/dmpk.25.134

DO - 10.2133/dmpk.25.134

M3 - Review article

C2 - 20460819

AN - SCOPUS:77952662988

VL - 25

SP - 134

EP - 148

JO - Drug Metabolism and Pharmacokinetics

JF - Drug Metabolism and Pharmacokinetics

SN - 1347-4367

IS - 2

ER -