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Energy metabolism in muscle

Basil T Darras, MD
Section Editor
Marc C Patterson, MD, FRACP
Deputy Editor
John F Dashe, MD, PhD


Patients with metabolic myopathies have underlying defects of energy production in muscle. Most affected patients have dynamic symptoms, such as exercise intolerance, muscle pain, and cramps upon exercise, rather than static symptoms, such as a fixed weakness of a specific muscle group.

To better understand these disorders, this topic review provides an overview of energy metabolism in muscle. The classification, diagnosis, and treatment of the metabolic myopathies are presented separately. (See "Approach to the metabolic myopathies" and "Metabolic myopathies caused by disorders of lipid and purine metabolism" and "Overview of inherited disorders of glucose and glycogen metabolism" and "Mitochondrial myopathies: Clinical features and diagnosis".)

Prior to a review of the pathways of energy metabolism, it is helpful to first briefly review the sources of energy in muscle.


The main types of "fuel" used by muscle for energy metabolism are glycogen, glucose, and free fatty acids [1-3]. The particular energy sources used by working muscle for aerobic metabolism depend upon a number of factors including the intensity, type, and duration of exercise, physical conditioning, and diet [4-6]:

  • At rest, muscle predominantly uses fatty acids [1].
  • During high-intensity, isometric exercise, anaerobic glycolysis, and the creatine kinase reaction, in which phosphocreatine is converted to adenosine triphosphate (ATP), are the primary sources of energy [2].
  • With submaximal exercise, the type of substrate used by muscle is heavily dependent upon the relative intensity of exercise. During low-intensity submaximal exercise, the main sources of energy are blood glucose and free fatty acids. With high-intensity submaximal exercise, the proportion of energy derived from glycogen and glucose is increased, and glycogen becomes the main source. Fatigue is experienced when glucose and glycogen stores are depleted (as when a marathon runner hits the "wall").


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Literature review current through: Oct 2015. | This topic last updated: Aug 21, 2013.
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  1. Felig P, Wahren J. Fuel homeostasis in exercise. N Engl J Med 1975; 293:1078.
  2. Wahren J. Glucose turnover during exercise in man. Ann N Y Acad Sci 1977; 301:45.
  3. Essén B. Intramuscular substrate utilization during prolonged exercise. Ann N Y Acad Sci 1977; 301:30.
  4. Gollnick PD, Piehl K, Saltin B. Selective glycogen depletion pattern in human muscle fibres after exercise of varying intensity and at varying pedalling rates. J Physiol 1974; 241:45.
  5. Essén B. Glycogen depletion of different fibre types in human skeletal muscle during intermittent and continuous exercise. Acta Physiol Scand 1978; 103:446.
  6. Das AM, Steuerwald U, Illsinger S. Inborn errors of energy metabolism associated with myopathies. J Biomed Biotechnol 2010; 2010:340849.
  7. Lithell H, Orlander J, Schéle R, et al. Changes in lipoprotein-lipase activity and lipid stores in human skeletal muscle with prolonged heavy exercise. Acta Physiol Scand 1979; 107:257.
  8. DiMauro, S, Tsujino, S. Nonlysosomal glycogenoses. In: Myology, Engel, A, Banker, B (Eds), McGraw-Hill, New York, 1994, p.1554.
  9. DiMauro, S, Tonin, P, Servidei, S. Metabolic myopathies. In: Handbook of Clinical Neurology, Rowland, L, DiMauro, S (Eds), Elsevier, Amsterdam, 1992, p. 479.
  10. DiMauro S, Miranda AF, Sakoda S, et al. Metabolic myopathies. Am J Med Genet 1986; 25:635.
  11. Lindinger MI, Heigenhauser GJ, McKelvie RS, Jones NL. Blood ion regulation during repeated maximal exercise and recovery in humans. Am J Physiol 1992; 262:R126.
  12. Lewis SF, Haller RG. The pathophysiology of McArdle's disease: clues to regulation in exercise and fatigue. J Appl Physiol (1985) 1986; 61:391.
  13. Lewis SF, Vora S, Haller RG. Abnormal oxidative metabolism and O2 transport in muscle phosphofructokinase deficiency. J Appl Physiol (1985) 1991; 70:391.
  14. DiMauro S, De Vivo D. Diseases of carbohydrate, fatty acid, and mitochondrial metabolism. In: Basic neurochemistry: Molecular, cellular, and medical aspects, 7th ed, Seigel G, Albers RW, Brady S, Price D. (Eds), Elsevier Academic Press, 2006. p.695.
  15. Taanman JW, Williams S. Structure and function of the mitochondrial oxidative phosphorylation system. In: Mitochondrial Disorders in Neurology 2, Schapira AHV, DiMauro S (Eds), Butterworth-Heinemann, Boston 2002. p.1.
  16. van Adel BA, Tarnopolsky MA. Metabolic myopathies: update 2009. J Clin Neuromuscul Dis 2009; 10:97.
  17. Fishbein WN. Myoadenylate deaminase deficiency: inherited and acquired forms. Biochem Med 1985; 33:158.
  18. Tein I. Lipid storage muscular disorders. In: Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician's Approach, Jones HR Jr, De Vivo DC, Darras BT (Eds), Butterworth Heinemann, Philadelphia 2003. p.833.
  19. Rubio-Gozalbo ME, Bakker JA, Waterham HR, Wanders RJ. Carnitine-acylcarnitine translocase deficiency, clinical, biochemical and genetic aspects. Mol Aspects Med 2004; 25:521.
  20. Tein I. Metabolic myopathies. Semin Pediatr Neurol 1996; 3:59.
  21. Hashimoto, T. Peroxisomal and mitochondrial enzymes. In: Progress in Clinical and Biological Research, Coates, P, Tanaka, K (Eds), Wiley, New York, NY 1992. p.19.
  22. Luo MJ, He XY, Sprecher H, Schulz H. Purification and characterization of the trifunctional beta-oxidation complex from pig heart mitochondria. Arch Biochem Biophys 1993; 304:266.
  23. Basic Neurochemistry: Molecular, Cellular and Medical Aspects, 7th, Brady S, Siegel G, Albers RW, Price DL (Eds), Elsevier Academic Press, Boston 2006.
  24. Darras BT, Friedman NR. Metabolic myopathies: a clinical approach; part I. Pediatr Neurol 2000; 22:87.
  25. Krahling JB, Gee R, Murphy PA, et al. Comparison of fatty acid oxidation in mitochondria and peroxisomes from rat liver. Biochem Biophys Res Commun 1978; 82:136.
  26. Kølvraa S, Gregersen N. Acyl-CoA:glycine N-acyltransferase: organelle localization and affinity toward straight- and branched-chained acyl-CoA esters in rat liver. Biochem Med Metab Biol 1986; 36:98.
  27. Roe CR, Millington DS, Maltby DA, et al. Diagnostic and therapeutic implications of medium-chain acylcarnitines in the medium-chain acyl-coA dehydrogenase deficiency. Pediatr Res 1985; 19:459.
  28. Baretz BH, Ramsdell HS, Tanaka K. Identification of n-hexanoylglycine in urines from two patients with Jamaican vomiting sickness. Clin Chim Acta 1976; 73:199.
  29. Millington D. New methods for the analysis of acylcarnitines and acyl-coenzyme A compounds. In: Mass Spectrometry in Biomedical Research, Gaskell S (Ed), John Wiley, New York 1986. p.97.