[14C]palmitate uptake in isolated rat liver mitochondria: effects of fasting, diabetes mellitus, and inhibitors of carnitine acyltransferase

J. M. Amatruda, D. H. Lockwood, S. Margolis, L. A. Kiesow

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Abstract

The rapid association of Na-[16-14C]palmitate with isolated rat liver mitochondria was measured by an oil separation method. This association was time- and temperature-dependent and was absolutely dependent on the presence of exogenous ATP and coenzyme A and partially dependent on exogenous carnitine. Carnitine dependence was enhanced at lower concentrations of [14C]palmitate. At 6.5 μM [14C]palmitate (molar ratio of palmitate to albumin equal to 0.54) the rate of association was linear for 20 sec and was increased more than 100% in the presence of carnitine. Carnitine-dependent association was inhibited by 2-bromo-palmitate, an inhibitor of carnitine acyltransferase I, but not by (+)-octanoylcarnitine, a presumed inhibitor of carnitine acyltransferase II. The association of [14C]palmitate with mitochondria was enhanced from 190 to 330% in mitochondria isolated from fasted animals and from 160 to 230% in mitochondria isolated from diabetic, ketotic animals as compared to control animals. The enhanced association with mitochondria from fasted animals was inhibited by 2-bromo-palmitate. These studies demonstrate a method of evaluating fatty acid association with mitochondria which, because of its dependence on carnitine and carnitine acyltransferase I activity, most likely represents true uptake into mitochondria. Furthermore, these studies indicate that the carnitine-dependent uptake of fatty acids into mitochondria is enhanced in the two ketotic states evaluated and that the carnitine acyltransferase system may be a regulatory site in ketone body production.

Original languageEnglish (US)
Pages (from-to)688-694
Number of pages7
JournalJournal of Lipid Research
Volume19
Issue number6
StatePublished - Jan 1 1978

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ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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