Relative importance of malonyl CoA and carnitine in maturation of fatty acid oxidation in newborn rabbit heart

A O Besikci, Fiona Margaret Campbell, T A Hopkins, J R B Dyck, G D Lopaschuk

    Research output: Contribution to journalArticle

    Abstract

    After birth, a dramatic increase in fatty acid oxidation occurs in the heart, which has been attributed to an increase in L-carnitine levels and a switch from the liver (L) to muscle (M) isoform of carnitine palmitoyltransferase (CPT)-1. However, because M-CPT-1 is more sensitive to inhibition by malonyl CoA, a potent endogenous regulator of fatty acid oxidation, a switch to the M-CPT-1 isoform should theoretically decrease fatty acid oxidation. Because of this discrepancy, we assessed the contributions of myocardial L-carnitine content and CPT-1 isoform expression and kinetics to the maturation of fatty acid oxidation in newborn rabbit hearts. Although fatty acid oxidation rates increased between 1 and 14 days after birth, myocardial L-carnitine concentrations did not increase. Changes in the expression of L-CPT-1 or M-CPT-1 mRNA after birth also did not parallel the increase in fatty acid oxidation. The K-m of CPT-1 for carnitine and the IC50 for malonyl CoA remained unchanged between 1 and 10 days after birth. However, malonyl CoA levels dramatically decreased, due in part to an increase in malonyl CoA decarboxylase activity. Our data suggest that a decrease in malonyl CoA control of CPT-1 is primarily responsible for the increase in fatty acid oxidation seen in the newborn heart.

    Original languageEnglish
    Pages (from-to)H283-H289
    Number of pages7
    JournalAmerican Journal of Physiology, Heart and Circulatory Physiology
    Volume284
    Issue number1
    DOIs
    Publication statusPublished - Jan 2003

    Keywords

    • carnitine palmitoyltransferase-1
    • pyruvate dehydrogenase
    • acetyl CoA carboxylase
    • glucose oxidation
    • ACTIVATED PROTEIN-KINASE
    • PALMITOYLTRANSFERASE-I
    • RAT-HEART
    • SKELETAL-MUSCLE
    • CARDIAC MYOCYTES
    • WORKING HEARTS
    • METABOLISM
    • DECARBOXYLASE
    • CARBOXYLASE
    • EXPRESSION
    • glucose oxidation
    • activated protein-kinase
    • palmitoyltransferase-I
    • rat-heart
    • skeletal-muscle
    • cardiac myocytes
    • working hearts
    • metabolism
    • decarboxylase
    • expression

    Cite this