Abstract
After birth, a dramatic increase in fatty acid oxidation occurs in the heart, which has been attributed to an increase in L-carnitine levels and a switch from the liver (L) to muscle (M) isoform of carnitine palmitoyltransferase (CPT)-1. However, because M-CPT-1 is more sensitive to inhibition by malonyl CoA, a potent endogenous regulator of fatty acid oxidation, a switch to the M-CPT-1 isoform should theoretically decrease fatty acid oxidation. Because of this discrepancy, we assessed the contributions of myocardial L-carnitine content and CPT-1 isoform expression and kinetics to the maturation of fatty acid oxidation in newborn rabbit hearts. Although fatty acid oxidation rates increased between 1 and 14 days after birth, myocardial L-carnitine concentrations did not increase. Changes in the expression of L-CPT-1 or M-CPT-1 mRNA after birth also did not parallel the increase in fatty acid oxidation. The K-m of CPT-1 for carnitine and the IC50 for malonyl CoA remained unchanged between 1 and 10 days after birth. However, malonyl CoA levels dramatically decreased, due in part to an increase in malonyl CoA decarboxylase activity. Our data suggest that a decrease in malonyl CoA control of CPT-1 is primarily responsible for the increase in fatty acid oxidation seen in the newborn heart.
Original language | English |
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Pages (from-to) | H283-H289 |
Number of pages | 7 |
Journal | American Journal of Physiology, Heart and Circulatory Physiology |
Volume | 284 |
Issue number | 1 |
DOIs | |
Publication status | Published - Jan 2003 |
Keywords
- carnitine palmitoyltransferase-1
- pyruvate dehydrogenase
- acetyl CoA carboxylase
- glucose oxidation
- ACTIVATED PROTEIN-KINASE
- PALMITOYLTRANSFERASE-I
- RAT-HEART
- SKELETAL-MUSCLE
- CARDIAC MYOCYTES
- WORKING HEARTS
- METABOLISM
- DECARBOXYLASE
- CARBOXYLASE
- EXPRESSION
- glucose oxidation
- activated protein-kinase
- palmitoyltransferase-I
- rat-heart
- skeletal-muscle
- cardiac myocytes
- working hearts
- metabolism
- decarboxylase
- expression