Reciprocal effects of 5-(tetradecyloxy)-2-furoic acid on fatty acid oxidation

David A. Otto, Chris Chatzidakis, Eva Kasziba, George Cook

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Under certain incubation conditions 5-(tetradecyloxy)-2-furoic acid (TOFA) stimulated the oxidation of palmitate by hepatocytes, as observed by others. A decrease in malonyl-CoA concentration accompanied the stimulation of oxidation. Under other conditions, however, TOFA inhibited fatty acid oxidation. The observed effects of TOFA depended on the TOFA and fatty acid concentrations, the cell concentration, the time of TOFA addition relative to the addition of fatty acid, and the nutritional state of the animal (fed or starved). The data indicate that only under limited incubation conditions may TOFA be used as an inhibitor of fatty acid synthesis without inhibition of fatty acid oxidation. When rat liver mitochondria were preincubated with TOFA, ketogenesis from palmitate was slightly inhibited (up to 20%) at TOFA concentrations that were less than that of CoA, but the inhibition became almost complete (up to 90%) when TOFA was greater than or equal to the CoA concentration. TOFA had only slight or no inhibitory effects on the oxidation of palmitoyl-CoA, palmitoyl(-)carnitine, or butyrate. Since TOFA can be converted to TOFyl-CoA, the data suggest that the inhibition of fatty acid oxidation from palmitate results from the decreased availability of CoA for extramitochondrial activation of fatty acids. These data, along with previous data of others, indicate that inhibition of fatty acid oxidation by CoA sequestration is a common mechanism of a group of carboxylic acid inhibitors. A general caution is appropriate with regard to the interpretation of results when using TOFA in studies of fatty acid oxidation.

Original languageEnglish (US)
Pages (from-to)23-31
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume242
Issue number1
DOIs
StatePublished - Jan 1 1985

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Fatty Acids
Oxidation
Coenzyme A
Palmitates
Fatty Acid Synthesis Inhibitors
2-furoic acid
5-(tetradecyloxy)-2-furancarboxylic acid
Palmitoyl Coenzyme A
Malonyl Coenzyme A
Mitochondria
Carnitine
Butyrates
Liver Mitochondrion
Carboxylic Acids
Liver
Rats
Hepatocytes
Animals
Chemical activation
Availability

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Reciprocal effects of 5-(tetradecyloxy)-2-furoic acid on fatty acid oxidation. / Otto, David A.; Chatzidakis, Chris; Kasziba, Eva; Cook, George.

In: Archives of Biochemistry and Biophysics, Vol. 242, No. 1, 01.01.1985, p. 23-31.

Research output: Contribution to journalArticle

Otto, David A. ; Chatzidakis, Chris ; Kasziba, Eva ; Cook, George. / Reciprocal effects of 5-(tetradecyloxy)-2-furoic acid on fatty acid oxidation. In: Archives of Biochemistry and Biophysics. 1985 ; Vol. 242, No. 1. pp. 23-31.
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abstract = "Under certain incubation conditions 5-(tetradecyloxy)-2-furoic acid (TOFA) stimulated the oxidation of palmitate by hepatocytes, as observed by others. A decrease in malonyl-CoA concentration accompanied the stimulation of oxidation. Under other conditions, however, TOFA inhibited fatty acid oxidation. The observed effects of TOFA depended on the TOFA and fatty acid concentrations, the cell concentration, the time of TOFA addition relative to the addition of fatty acid, and the nutritional state of the animal (fed or starved). The data indicate that only under limited incubation conditions may TOFA be used as an inhibitor of fatty acid synthesis without inhibition of fatty acid oxidation. When rat liver mitochondria were preincubated with TOFA, ketogenesis from palmitate was slightly inhibited (up to 20{\%}) at TOFA concentrations that were less than that of CoA, but the inhibition became almost complete (up to 90{\%}) when TOFA was greater than or equal to the CoA concentration. TOFA had only slight or no inhibitory effects on the oxidation of palmitoyl-CoA, palmitoyl(-)carnitine, or butyrate. Since TOFA can be converted to TOFyl-CoA, the data suggest that the inhibition of fatty acid oxidation from palmitate results from the decreased availability of CoA for extramitochondrial activation of fatty acids. These data, along with previous data of others, indicate that inhibition of fatty acid oxidation by CoA sequestration is a common mechanism of a group of carboxylic acid inhibitors. A general caution is appropriate with regard to the interpretation of results when using TOFA in studies of fatty acid oxidation.",
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