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

Research output: Contribution to journalArticle

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Abstract

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
Volume270
Issue number15
DOIs
StatePublished - 1995

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Carnitine O-Palmitoyltransferase
Rats
Protein Isoforms
Carnitine
Accidental Falls
Animals
Newborn Animals
Ethylene Oxide
Mitochondria
Carboxylic Acids
Liver
Membrane Proteins
Muscle
Fatty Acids

ASJC Scopus subject areas

  • Biochemistry

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Mitochondrial carnitine palmitoyltransferase I isoform switching in the developing rat heart. / Brown, N. F.; Weis, B. C.; Husti, J. E.; Foster, D. W.; McGarry, J. D.

In: Journal of Biological Chemistry, Vol. 270, No. 15, 1995, p. 8952-8957.

Research output: Contribution to journalArticle

Brown, N. F. ; Weis, B. C. ; Husti, J. E. ; Foster, D. W. ; McGarry, J. D. / Mitochondrial carnitine palmitoyltransferase I isoform switching in the developing rat heart. In: Journal of Biological Chemistry. 1995 ; Vol. 270, No. 15. pp. 8952-8957.
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abstract = "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.",
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