Observations on the affinity for carnitine, and malonyl-CoA sensitivity, of carnitine palmitoyltransferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat

J. D. McGarry, S. E. Mills, C. S. Long, D. W. Foster

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436 Scopus citations

Abstract

The requirement for carnitine and the malonyl-CoA sensitivity of carnitine palmitoyltransferase I (EC 2.3.1.21) were measured in isolated mitochondria from eight tissues of animal or human origin using fixed concentrations of palmitoyl-CoA (50 μM) and albumin (147 μM). The Km for carnitine spanned a 20-fold range, rising from about 35 μM in adult rat and human foetal liver to 700 μM in dog heart. Intermediate values of increasing magnitude were found for rat heart, guinea pig liver and skeletal muscle of rat, dog, and man. Conversely, the concentration of malonyl-CoA required for 50% suppression of enzyme activity fell from the region of 2-3 μM in human and rat liver to only 20 nM in tissues displaying the highest Km for carnitine. Thus, the requirement for carnitine and sensitivity to malonyl-CoA appeared to be inversely related. The Km of carnitine palmitoyltransferase I for palmitoyl-CoA was similar in tissues showing large differences in requirement for carnitine. Other experiments established that, in addition to liver, heart and skeletal muscle of fed rats contain significant quantities of malonyl-CoA and that in all three tissues the level falls with starvation. Although its intracellular location in heart and skeletal muscle is not known, the possibility is raised that malonyl-CoA (or a related compound) could, under certain circumstances, interact with carnitine palmitoyltransferase I in non-hepatic tissues and thereby exert control over long chain fatty acid oxidation.

Original languageEnglish (US)
Pages (from-to)21-28
Number of pages8
JournalBiochemical Journal
Volume214
Issue number1
DOIs
StatePublished - Jan 1 1983

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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