Relative importance of malonyl CoA and carnitine in maturation of fatty acid oxidation in newborn rabbit heart.
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 IC(50) 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.
Onay-Besikci
Arzu
A
Department of Pharmacology, University of Alberta, Edmonton, Canada T6G 2S2.
Campbell
Fiona M
FM
Hopkins
Teresa A
TA
Dyck
Jason R B
JR
Lopaschuk
Gary D
GD
Onay Besikci
Arzu
A
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development* / Q000378:metabolism*; D002331:Carnitine / Q000502:physiology*; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics; D005227:Fatty Acids / Q000378:metabolism* / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000235:genetics; D007700:Kinetics; D008316:Malonyl Coenzyme A / Q000502:physiology*; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits
D005227:Fatty Acids; D007527:Isoenzymes; D012333:RNA, Messenger; D008316:Malonyl Coenzyme A; D002334:Carnitine O-Palmitoyltransferase; D005947:Glucose; D002331:Carnitine