Mechanism responsible for aminooxyacetate and glycolate stimulation of ethanol oxidation by isolated hepatocytes

Robert A. Harris, Neal W. Cornell, Christopher Straight, Richard L. Veech

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Aminooxyacetate (H2NOCH2CO2-) is known to inhibit ethanol oxidation by blocking transamination reactions required for the transport of reducing equivalents from the cytosol to the mitosol. Ethanol oxidation is stimulated, however, when high concentrations of aminooxyacetate are used. This paradoxical stimulation of ethanol oxidation by aminooxyacetate has been resolved. Aminooxyacetate is metabolized to glycolate and glyoxylate. Glycolate stimulates ethanol oxidation in part by providing H2O2 for catalase-mediated ethanol oxidation. Evidence was also found, however, for a glycolate-glyoxylate shuttle for the transport of reducing equivalents between the cytosol and the peroxisomes. d,l-2-Hydroxy-3-butynoate, an inhibitor of peroxisomal glycolate oxidation, blocks the stimulation of ethanol oxidation caused by glycolate or aminooxyacetate. The stimulation of ethanol oxidation by these compounds shows partial sensitivity to 4-pentylpyrazole or 3-aminotriazole, indicating that both alcohol dehydrogenase (EC 1.1.1.1) and catalase (EC 1.11.1.6) are involved. Glyoxylate stimulates ethanol oxidation, and its conversion to glycolate is dependent on ethanol. Although it appears that a glycolate-glyoxylate shuttle for reoxidation of cytosolic NADH can be readily established in vitro, no evidence was found for the existence of this shuttle in vivo. Ethyl hydrazinoacetate has been proposed as a substitute for aminooxyacetate in metabolic studies; however, enzymatic hydrolysis of this compound to give ethanol limits its usefulness as an inhibitor of ethanol oxidation. 2-Aminooxypropionate does not show the paradoxical stimulation of ethanol oxidation. Its effectiveness in inhibiting aspartate aminotransferase (EC 2.6.1.1) is similar to that for aminooxyacetate. Thus, 2-aminooxypropionate appears to be a good alternative to aminooxyacetate in metabolic studies in vivo, in perfused liver or in isolated cells.

Original languageEnglish (US)
Pages (from-to)414-425
Number of pages12
JournalArchives of Biochemistry and Biophysics
Volume213
Issue number2
DOIs
StatePublished - Feb 1982
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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