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

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1649-1656
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume345
Issue number4
DOIs
Publication statusPublished - Jul 14 2006

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Glucuronosyltransferase
Acyl Coenzyme A
Chemical activation
Cetomacrogol
Hymecromone
Nitrobenzoates
Membranes
Ethylmaleimide
Microsomes
Endoplasmic Reticulum
Rats
Digestion
Permeability
Modulation
oleoyl-coenzyme A
Liver

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Fatty acyl-CoA as an endogenous activator of UDP-glucuronosyltransferases. / Okamura, Kazuharu; Ishii, Yuji; Ikushiro, Shin ichi; Mackenzie, Peter I.; Yamada, Hideyuki.

In: Biochemical and Biophysical Research Communications, Vol. 345, No. 4, 14.07.2006, p. 1649-1656.

Research output: Contribution to journalArticle

Okamura, Kazuharu ; Ishii, Yuji ; Ikushiro, Shin ichi ; Mackenzie, Peter I. ; Yamada, Hideyuki. / Fatty acyl-CoA as an endogenous activator of UDP-glucuronosyltransferases. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 345, No. 4. pp. 1649-1656.
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