Two mechanisms produce tissue-specific inhibition of fatty acid oxidation by oxfenicine

T. W. Stephens, A. J. Higgins, G. A. Cook, Robert Harris

Research output: Contribution to journalArticle

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Abstract

Oxfenicine [S-2-(4-hydroxyphenyl)glycine] is transaminated in heart and liver to 4-hydroxyphenylglyoxylate, an inhibitor of fatty acid oxidation shown in this study to act at the level of carnitine palmitoyltransferase I (EC 2.3.1.21). Oxfenicine was an effective inhibitor of fatty acid oxidation in heart, but not in liver. Tissue specificity of oxfenicine inhibition of fatty acid oxidation was due to greater oxfenicine transaminase activity in heart and to greater sensitivity of heart carnitine palmitoyltransferase I to inhibition by 4-hydroxyphenylglyoxylate [I50 (concentration giving 50% inhibition) of 11 and 510 μM for the enzymes of heart and liver mitochondria, respectively]. Branched-chain-amino-acid aminotransferase (isoenzyme I, EC 2.6.1.42) was responsible for the transamination of oxfenicine in heart. A positive correlation was found between the capacity of various tissues to transaminate oxfenicine and the known content of branched-chain-amino-acid aminotransferase in these tissues. Out of three observed liver oxfenicine aminotransferase activities, one may correspond to asparagine aminotransferase, but the major activity could not be identified by partial purification and characterization. As reported previously for malonyl-CoA inhibition of carnitine palmitoyltransferase I, 4-hydroxyphenylglyoxylate inhibition of this enzyme was found to be very pH-dependent. In striking contrast with the kinetics of malonyl-CoA inhibition, 4-hydroxyphenylglyoxylate inhibition was not affected by oleoyl-CoA concentration, but was partially reversed by increasing carnitine concentrations.

Original languageEnglish
Pages (from-to)651-660
Number of pages10
JournalBiochemical Journal
Volume227
Issue number2
StatePublished - 1985

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Fatty Acids
Tissue
Oxidation
Carnitine O-Palmitoyltransferase
Liver
Malonyl Coenzyme A
serine-glyoxylate aminotransferase
Corrosion inhibitors
Transaminases
Heart Mitochondria
Organ Specificity
Mitochondria
Carnitine
Liver Mitochondrion
Enzymes
4-hydroxyphenylglycine
Glycine
Isoenzymes
Purification
Kinetics

ASJC Scopus subject areas

  • Biochemistry

Cite this

Two mechanisms produce tissue-specific inhibition of fatty acid oxidation by oxfenicine. / Stephens, T. W.; Higgins, A. J.; Cook, G. A.; Harris, Robert.

In: Biochemical Journal, Vol. 227, No. 2, 1985, p. 651-660.

Research output: Contribution to journalArticle

Stephens, T. W. ; Higgins, A. J. ; Cook, G. A. ; Harris, Robert. / Two mechanisms produce tissue-specific inhibition of fatty acid oxidation by oxfenicine. In: Biochemical Journal. 1985 ; Vol. 227, No. 2. pp. 651-660.
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