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Commentary

Cytosolic reverse CrAT activity in cardiac tissue: potential importance for fuel selection

Heather L. Petrick, Graham P. Holloway
Biochemical Journal Apr 09, 2018, 475 (7) 1267-1269; DOI: 10.1042/BCJ20180121
Heather L. Petrick
Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
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Graham P. Holloway
Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada
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  • For correspondence: ghollowa@uoguelph.ca
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  • Cytosolic carnitine acetyltransferase as a source of cytosolic acetyl-CoA: a possible mechanism for regulation of cardiac energy metabolism

Abstract

The movement of lipids across mitochondrial membranes represents a rate-limiting step in fatty acid oxidation within the heart. A key regulatory point in this process is flux through carnitine palmitoyltransferase-I (CPT-I), an enzyme located on the outer mitochondrial membrane. Malonyl-CoA (M-CoA) is a naturally occurring inhibitor of CPT-I; therefore, the abundance of M-CoA has long been considered a major regulator of fatty acid oxidation. A recent paper published in the Biochemical Journal by Altamimi et al. (Biochem. J. (2018) 475, 959–976) provides evidence for a novel mechanism to produce M-CoA. Specifically, these authors identified carnitine acetyltransferase within the cytosol and further show that flux in the reverse direction forms acetyl-CoA, which is the necessary substrate for the subsequent synthesis of M-CoA. The elegant study design and intriguing data presented by Altamimi et al. provide further insights into the reciprocal regulation of substrate selection within the heart, with implications for fuel utilization and the development of cardiac diseases.

  • carnitine acyltransferases
  • Abbreviations

    ACC,
    acetyl-CoA carboxylase;
    ACL,
    ATP citrate lyase;
    CPT-I,
    carnitine palmitoyltransferase-I;
    CrAT,
    carnitine acetyltransferase;
    M-CoA,
    malonyl-CoA;
    rCrAT,
    reverse carnitine acetyltransferase activity;
    TCA,
    tricarboxylic acid cycle
    • © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
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    April 2018

    Volume: 475 Issue: 7

    Biochemical Journal: 475 (7)
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    Cytosolic reverse CrAT activity in cardiac tissue: potential importance for fuel selection
    Heather L. Petrick, Graham P. Holloway
    Biochemical Journal Apr 2018, 475 (7) 1267-1269; DOI: 10.1042/BCJ20180121
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    Cytosolic reverse CrAT activity in cardiac tissue: potential importance for fuel selection
    Heather L. Petrick, Graham P. Holloway
    Biochemical Journal Apr 2018, 475 (7) 1267-1269; DOI: 10.1042/BCJ20180121

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    Keywords

    carnitine acyltransferases

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