Mitochondrial carnitine palmitoyltransferase I isoform switching in the developing rat heart

N. F. Brown, B. C. Weis, J. E. Husti, D. W. Foster, J. D. McGarry

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138 Scopus citations


The expression pattern of mitochondrial carnitine palmitoyltransferase (CPT) enzymes was examined in the developing rat heart. Whereas the specific activity of CPT II increased ~3-fold during the first month of life, the profile for CPT I, which is composed of both liver (L) and muscle (M) isoforms, was more complex. Exposure of mitochondria to [3H]etomoxir (a covalent ligand for CPT I), followed by fluorographic analysis of the membrane proteins, established that while in the adult heart L-CPT I represents a very minor constituent, its contribution is much greater in the newborn animal. Use of the related inhibitor, 2-[6-(2,4- dinitrophenoxy)hexyl]oxirane-2-carboxylic acid (specific for L-CPT I), allowed the activities of the two CPT I variants to be quantified separately. The results showed that in the neonatal heart, L-CPT I contributes ~25% to total CPT I activity (in V(max) terms), the value falling during growth of the pups (with concomitant increasing expression of the M isoform) to its adult level of 2-3%. Because the myocardial carnitine content is very low at birth and rises dramatically over the next several weeks, it can he estimated that L-CPT I (K(m) for carnitine of only 30 μM compared with a value of 500 μM for M-CPT I) is responsible for some 60% of total cardiac fatty acid oxidation in the newborn rat; the value falls to ~4% in adult animals. Should these findings have a parallel in humans, they could have important implications for understanding the pathophysiological consequences of inherited L-CPT I deficiency syndromes.

Original languageEnglish (US)
Pages (from-to)8952-8957
Number of pages6
JournalJournal of Biological Chemistry
Issue number15
StatePublished - 1995

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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