Fatty acyl-CoA as an endogenous activator of UDP-glucuronosyltransferases

Kazuharu Okamura, Yuji Ishii, Shin ichi Ikushiro, Peter I. Mackenzie, Hideyuki Yamada

研究成果: Contribution to journalArticle査読

11 被引用数 (Scopus)

抄録

The acyl-CoA-dependent modulation of hepatic microsomal UDP-glucuronosyltransferase (UGT) function in rats was studied. Oleoyl- and palmitoyl-CoAs inhibited UGT activity toward 4-methylumbelliferone in the presence of Brij 58. However, acyl-CoAs enhanced UGT activity in untreated microsomes. A maximum activation of about 8-fold over the control was observed at 15 μM oleoyl-CoA, whereas 50 μM or more oleoyl-CoA had an inhibitory effect on UGT function. Medium- and long-chain acyl-CoAs also exhibited similar effects. On the basis of resistance to tryptic digestion of UGTs, oleoyl-CoA at 15 μM has no ability to change the permeability of the endoplasmic reticulum (ER) membrane, although perturbation of the membrane occurred with 50 μM oleoyl-CoA. N-Ethylmaleimide and 5,5′-dithiobis(2-nitrobenzoic acid) abolished the oleoyl-CoA (15 μM)-dependent activation of microsomal UGT. These results suggest that: (1) acyl-CoAs play a role as an endogenous activator of UGTs, and (2) a sulfhydryl group is required for the activation of UGT by physiological concentrations of acyl-CoAs.

本文言語英語
ページ(範囲)1649-1656
ページ数8
ジャーナルBiochemical and Biophysical Research Communications
345
4
DOI
出版ステータス出版済み - 7 14 2006

All Science Journal Classification (ASJC) codes

  • 生物理学
  • 生化学
  • 分子生物学
  • 細胞生物学

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