Relative importance of malonyl CoA and carnitine in maturation of fatty acid oxidation in newborn rabbit heart

Besikci A., Campbell F., Hopkins T., Dyck J., Lopaschuk G.

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, cilt.284, sa.1, 2003 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 284 Sayı: 1
  • Basım Tarihi: 2003
  • Doi Numarası: 10.1152/ajpheart.00461.2002
  • Dergi Adı: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: 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
  • Ankara Üniversitesi Adresli: Evet

Özet

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.