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Regulation of carbohydrate and fatty acid utilization by L-carnitine during cardiac development and hypoxia

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Abstract

This study is designed to investigate whether substrate preference in the myocardium during the neonatal period and hypoxia-induced stress is controlled intracellularly or by extracellular substrate availability. To determine this, the effect of exogenous L-carnitine on the regulation of carbohydrate and fatty acid metabolism was determined during cardiac stress (hypoxia) and during the postnatal period. The effect of L-carnitine on long chain (palmitate) and medium chain (octonoate) fatty acid oxidation was studied in cardiac myocytes isolated from less than 24 h old (new born; NB), 2 week old (2 week) and hypoxic 4 week old (HY) piglets. Palmitate oxidation was severely decreased in NB cells compared to those from 2 week animals (0.456 ± 0.04 vs. 1.207 ± 0.52 nmol/mg protein/30 min); surprisingly, cells from even older hypoxic animals appeared shifted toward the new born state (0.695 ± 0.038 nmol/mg protein/30 min). Addition of L-carnitine to the incubation medium, which stimulates carnitine palmitoyl-transferase I (CPTI) accelerated palmitate oxidation 3 fold in NB and approximately 2 fold in HY and 2 week cells. In contrast, octanoate oxidation which was greater in new born myocytes than in 2 week cells, was decreased by L-carnitine suggesting a compensatory response. Furthermore, oxidation of carbohydrates (glucose, pyruvate, and lactate) was greatly increased in new born myocytes compared to 2 week and HY cells and was accompanied by a parallel increase in pyruvate dehydrogenase (PDH) activity. The concentration of malonyl-CoA, a potent inhibitor of CPTI was significantly higher in new born heart than at 2 weeks. These metabolic data taken together suggest that intracellular metabolic signals interact to shift from carbohydrate to fatty acid utilization during development of the myocardium. The decreased oxidation of palmitate in NB hearts probably reflects decreased intracellular L-carnitine and increased malonyl-CoA concentrations. Interestingly, these data further suggest that the cells remain compliant so that under stressful conditions, such as hypoxia, they can revert toward the neonatal state of increased glucose utilization.

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References

  1. Neely JR, Morgan HE: Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. Annu Rev Physiol 36: 413–459, 1974

    Google Scholar 

  2. Saddik M, Lopaschuk GD: Myocardial triglyceride turnover and contribution to energy substrate utilization in isolated working rat heart. J Biol Chem 266: 8162–8170, 1991

    Google Scholar 

  3. Paulson DJ, Grass MF: Endogenous triacylglycerol metabolism in diabetic heart. Am J Physiol 242: H1084–H1094, 1982

    Google Scholar 

  4. Lopaschuk GD, Spafford MA, Marsh DR: Glycolysis is predominant source of myocardial ATP production immediately after birth. Am J Physiol 261: H1698–1705, 1991

    Google Scholar 

  5. Medina JM: The role of lactates as energy substrate for brain during the early neonatal period. Biol Neonate 48: 237–244, 1985

    Google Scholar 

  6. Phelps RL, Metzger BE, Freinkel N: Carbohydrate metabolism in pregnancy. Χ VII. Diurnal profiles of plasma glucose, insulin, free fatty acids, triglycerides, cholesterol, and individual acids in the late normal pregnancy. Am J Obstet Gynecol 140: 730–736, 1981

    Google Scholar 

  7. Goodwin CW, Mela L, Deutsch C, Forster RE, Miller LD, Delivoria-Papadopoulous M: Development and adaptation of heart mitochondria respiratory chain function in fetus and new born. Adv Exp Med Biol 75: 713–719, 1976

    Google Scholar 

  8. Glatz JFC, Veerkamp JH: Postnatal development of palmitate oxidation and mitochondrial enzyme activities in rat cardiac and skeletal muscle. Biochim Biophys Acta 711: 327–335, 1982

    Google Scholar 

  9. Tomec RJ, Hoppel CL: Carnitine palmitoyltransferase in bovine fetal heart mitochondria. Arch Biochem Biophys 170: 716–723, 1975

    Google Scholar 

  10. Prip-Buss C, Pegorier JP, Duee PH, Kohl C, Girard J: Evidence that the sensitivity of carnitine palmitoyltransferase I to inhibition by malonyl-CoA is an important site of regulation of hepatic fatty acid oxidation in the fetal and new born heart. Biochem J 269: 409–415, 1990

    Google Scholar 

  11. Brown NF, Weis BC, Husti JE, Foster DW, McGarry JD: Mitochondrial carnitine palmitoyltransferase I isoform switching in the developing rat heart. J Biol Chem 270: 8952–8957, 1995

    Google Scholar 

  12. Fisher DJ: Left ventricular oxygen consumption and function in hypoxia in conscious lambs. Am J Physiol 244: H664–H671, 1983

    Google Scholar 

  13. Genner G: Influence of hypoxia and glucose on contractility of papillary muscles from adult and neonatal rabbits. Biol Neonate 21: 90–106, 1972

    Google Scholar 

  14. Jarmakani JM, Nakazawa M, Nagatomo T, Langer GA: Effect of hypoxia on myocardial high energy phosphates in the neonatal mammalian heart. Am J Physiol 235: H475–481, 1978

    Google Scholar 

  15. Su JY, Friedman WF: Comparison of the response of fetal and adult cardiac muscle to hypoxia. Am J Physiol 244: 1249–1253, 1973

    Google Scholar 

  16. Owen P, Dennis S, Opie LH: Glucose flux rate regulates onset of ischemic contracture in globally underperfused rat hearts. Circ Res 66: 344–54, 1990

    Google Scholar 

  17. Jeremy RW, Ambrosia G, Pike MM, Jacobus WE, Becker LC: The functional recovery of post-ischemic myocardium requires glycolysis during early reperfusion. J Mol Cell Cardiol 25: 261–276, 1993

    Google Scholar 

  18. Frangakis CJ, Bahl JJ, Mc Daniel H, Bressler R: Tolerance to physiological calcium by isolated myocytes from the adult rat heart: An improved cellular preparation, Life Sci 27: 815–825, 1980

    Google Scholar 

  19. King MT, Reiss PD, Cornell NW. Determination of short-chain coenzyme A compounds by reversed-phase high performance liquid chromatography. Meth Enzymol 166: 70–79, 1988

    Google Scholar 

  20. Millington DS, Kodo N, Terada N, Roe D, Chase DH: The analysis of diagnostic markers of genetic disorders in human blood and urine using tandem mass spectrometry with liquid secondary ion mass spectrometry. Int J Mass Spectrom Ion Proc 111: 211–228, 1991

    Google Scholar 

  21. Fritz IB: Action of carnitine on long chain fatty acid oxidation by liver. Am J Physiol 197: 297–304, 1959

    Google Scholar 

  22. McGarry JD, Woeltje KF, Kuwajima M, Foster DW: Regulation of ketogenesis and the renaissance of carnitine palmitoyl transferase. Diabetes Metab Rev 5: 271–284, 1989

    Google Scholar 

  23. Schulz H: In: DE Vance, JE Vance (eds). Biochemistry of Lipids and Membranes. Benjamin-Cummings, Menlo Park, CA, 1985, pp 116–142

    Google Scholar 

  24. Itoi T: Metabolic changes in the developing heart muscle of mice –the palmitate oxidation under physiological enviroment. J Japan Pediatr Soc 92: 1879–1888, 1988

    Google Scholar 

  25. Wieland OH: The mammalian pyruvate dehydrogenase complex: structure and regulation. Rev Physiol Biochem Pharmacol 95: 123–170, 1983

    Google Scholar 

  26. Broderick TL, Quinney HA, Lopaschuk GD: Carnitine stimulation of glucose oxidation in the fatty acid perfused isolated working heart. J Biol Chem 267: 3758–3763, 1992

    Google Scholar 

  27. Abdel-aleem S, Sayed-Ahmed M, Nada M, Hendrickson SC, St. Louis J, Walthhall HP, Lowe JE: Regulation of fatty acid oxidation by acetyl-CoA generated from glucose utilization in isolated myocytes. J Mol Cell Cardiol 28: 825–833, 1996

    Google Scholar 

  28. Rolph TP, Jones CT. Regulation of glycolytic flux in the heart of the fetal guinea-pig. J Dev Physiol 5831–5849, 1983

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Authors and Affiliations

  1. Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA

    Salah Abdel-aleem, James St. Louis, Steven C. Hendrickson, Hesham M. El-Shewy, Khalifa El-Dawy & James E. Lowe

  2. Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA

    Doris A. Taylor

Authors
  1. Salah Abdel-aleem
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  2. James St. Louis
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  3. Steven C. Hendrickson
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  4. Hesham M. El-Shewy
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  5. Khalifa El-Dawy
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  6. Doris A. Taylor
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  7. James E. Lowe
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Abdel-aleem, S., St. Louis, J., Hendrickson, S.C. et al. Regulation of carbohydrate and fatty acid utilization by L-carnitine during cardiac development and hypoxia. Mol Cell Biochem 180, 95–103 (1998). https://doi.org/10.1023/A:1006843107922

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  • DOI: https://doi.org/10.1023/A:1006843107922

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