title: Mitochondrial carnitine palmitoyltransferase I isoform switching in the developing rat heart.
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 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.
authors.affiliation: Department of Internal Medicine, University of Texas Southwestern Medical Center, Southwestern Medical School, Dallas 75235, USA.
authors.forename: N F
authors.initials: NF
authors.lastname: Brown
authors.forename: B C
authors.initials: BC
authors.lastname: Weis
authors.forename: J E
authors.initials: JE
authors.lastname: Husti
authors.forename: D W
authors.initials: DW
authors.lastname: Foster
authors.forename: J D
authors.initials: JD
authors.lastname: McGarry
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006321:Heart / Q000196:embryology* / Q000254:growth & development; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007527:Isoenzymes; D002334:Carnitine O-Palmitoyltransferase