Ethanol and oleate inhibition of α-ketoisovalerate and 3-hydroxyisobutyrate metabolism by isolated hepatocytes

Hongyu Hu, Jerzy A. Jaskiewicz, Robert Harris

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Ethanol inhibited glucose synthesis from α-ketoisovalerate by isolated rat hepatocytes without significant inhibition of flux through the branched-chain α-ketoacid dehydrogenase complex. Accumulation of 3-hydroxyisobutyrate, an intermediate in the catabolism of α-ketoisovalerate, was increased by ethanol, indicating inhibition of flux at the level of 3-hydroxyisobutyrate dehydrogenase. 3-Hydroxybutyrate caused the same effects as ethanol, suggesting inhibition was a consequence of an increase in the mitochondrial NADH/NAD+ ratio. Flux through the 3-hydroxyisobutyrate dehydrogenase was more sensitive to regulation by the mitochondrial NADH/ NAD+ ratio than flux through the branched-chain α-ketoacid dehydrogenase. Oleate also inhibited glucose synthesis from α-ketoisovalerate, but marked inhibition of flux through the branched-chain α-ketoacid dehydrogenase complex was caused by this substrate.

Original languageEnglish
Pages (from-to)57-62
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume299
Issue number1
DOIs
StatePublished - Nov 15 1992

Fingerprint

Enzyme inhibition
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
3-hydroxyisobutyrate dehydrogenase
Oleic Acid
Metabolism
NAD
Hepatocytes
Ethanol
Fluxes
Glucose
3-Hydroxybutyric Acid
Rats
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Ethanol and oleate inhibition of α-ketoisovalerate and 3-hydroxyisobutyrate metabolism by isolated hepatocytes. / Hu, Hongyu; Jaskiewicz, Jerzy A.; Harris, Robert.

In: Archives of Biochemistry and Biophysics, Vol. 299, No. 1, 15.11.1992, p. 57-62.

Research output: Contribution to journalArticle

@article{6637b4e9b315436f8f51205c4c7dbe09,
title = "Ethanol and oleate inhibition of α-ketoisovalerate and 3-hydroxyisobutyrate metabolism by isolated hepatocytes",
abstract = "Ethanol inhibited glucose synthesis from α-ketoisovalerate by isolated rat hepatocytes without significant inhibition of flux through the branched-chain α-ketoacid dehydrogenase complex. Accumulation of 3-hydroxyisobutyrate, an intermediate in the catabolism of α-ketoisovalerate, was increased by ethanol, indicating inhibition of flux at the level of 3-hydroxyisobutyrate dehydrogenase. 3-Hydroxybutyrate caused the same effects as ethanol, suggesting inhibition was a consequence of an increase in the mitochondrial NADH/NAD+ ratio. Flux through the 3-hydroxyisobutyrate dehydrogenase was more sensitive to regulation by the mitochondrial NADH/ NAD+ ratio than flux through the branched-chain α-ketoacid dehydrogenase. Oleate also inhibited glucose synthesis from α-ketoisovalerate, but marked inhibition of flux through the branched-chain α-ketoacid dehydrogenase complex was caused by this substrate.",
author = "Hongyu Hu and Jaskiewicz, {Jerzy A.} and Robert Harris",
year = "1992",
month = "11",
day = "15",
doi = "10.1016/0003-9861(92)90243-P",
language = "English",
volume = "299",
pages = "57--62",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Ethanol and oleate inhibition of α-ketoisovalerate and 3-hydroxyisobutyrate metabolism by isolated hepatocytes

AU - Hu, Hongyu

AU - Jaskiewicz, Jerzy A.

AU - Harris, Robert

PY - 1992/11/15

Y1 - 1992/11/15

N2 - Ethanol inhibited glucose synthesis from α-ketoisovalerate by isolated rat hepatocytes without significant inhibition of flux through the branched-chain α-ketoacid dehydrogenase complex. Accumulation of 3-hydroxyisobutyrate, an intermediate in the catabolism of α-ketoisovalerate, was increased by ethanol, indicating inhibition of flux at the level of 3-hydroxyisobutyrate dehydrogenase. 3-Hydroxybutyrate caused the same effects as ethanol, suggesting inhibition was a consequence of an increase in the mitochondrial NADH/NAD+ ratio. Flux through the 3-hydroxyisobutyrate dehydrogenase was more sensitive to regulation by the mitochondrial NADH/ NAD+ ratio than flux through the branched-chain α-ketoacid dehydrogenase. Oleate also inhibited glucose synthesis from α-ketoisovalerate, but marked inhibition of flux through the branched-chain α-ketoacid dehydrogenase complex was caused by this substrate.

AB - Ethanol inhibited glucose synthesis from α-ketoisovalerate by isolated rat hepatocytes without significant inhibition of flux through the branched-chain α-ketoacid dehydrogenase complex. Accumulation of 3-hydroxyisobutyrate, an intermediate in the catabolism of α-ketoisovalerate, was increased by ethanol, indicating inhibition of flux at the level of 3-hydroxyisobutyrate dehydrogenase. 3-Hydroxybutyrate caused the same effects as ethanol, suggesting inhibition was a consequence of an increase in the mitochondrial NADH/NAD+ ratio. Flux through the 3-hydroxyisobutyrate dehydrogenase was more sensitive to regulation by the mitochondrial NADH/ NAD+ ratio than flux through the branched-chain α-ketoacid dehydrogenase. Oleate also inhibited glucose synthesis from α-ketoisovalerate, but marked inhibition of flux through the branched-chain α-ketoacid dehydrogenase complex was caused by this substrate.

UR - http://www.scopus.com/inward/record.url?scp=0026453165&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026453165&partnerID=8YFLogxK

U2 - 10.1016/0003-9861(92)90243-P

DO - 10.1016/0003-9861(92)90243-P

M3 - Article

C2 - 1444452

AN - SCOPUS:0026453165

VL - 299

SP - 57

EP - 62

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

IS - 1

ER -