Mitochondrial carnitine palmitoyltransferase I isoform switching in the developing rat heart.
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.
Brown
N F
NF
Department of Internal Medicine, University of Texas Southwestern Medical Center, Southwestern Medical School, Dallas 75235, USA.
Weis
B C
BC
Husti
J E
JE
Foster
D W
DW
McGarry
J D
JD
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
D007527:Isoenzymes; D002334:Carnitine O-Palmitoyltransferase