Mitochondrial Carnitine Palmitoyltransferase I Isoform Switching in the Developing Rat Heart
| Autor: | Daniel W. Foster, N. F. Brown, J. E. Husti, B C Weis, J. D. McGarry |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Aging endocrine system medicine.medical_specialty endocrine system diseases Mitochondrion Biology Biochemistry Isozyme Mitochondria Heart Rats Sprague-Dawley chemistry.chemical_compound Internal medicine medicine Animals heterocyclic compounds Carnitine Carnitine O-palmitoyltransferase neoplasms Molecular Biology Beta oxidation Cells Cultured Carnitine O-Palmitoyltransferase Myocardium Heart Cell Biology digestive system diseases Rats Isoenzymes Kinetics Endocrinology chemistry Female Specific activity Carnitine palmitoyltransferase I Etomoxir medicine.drug |
| Zdroj: | Journal of Biological Chemistry. 270:8952-8957 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.270.15.8952 |
| Popis: | The expression pattern of mitochondrial carnitine palmitoyltransferase (CPT) enzymes was examined in the developing rat heart. Whereas the specific activity of CPT II increased approximately 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 approximately 25% to total CPT I activity (in Vmax 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 be estimated that L-CPT I (Km for carnitine of only 30 microM compared with a value of 500 microM for M-CPT I) is responsible for some 60% of total cardiac fatty acid oxidation in the newborn rat; the value falls to approximately 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. |
| Databáze: | OpenAIRE |
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