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Three classes of metabolic diseases of muscle are recognized—one is traceable to a primary, or hereditary, metabolic abnormality of the muscle itself; another in which the myopathy is secondary to a disorder of endocrine function, i.e., to disease of the thyroid, parathyroid, pituitary, or adrenal gland; and a third group that is the result of a large variety of myotoxic drugs and other chemical agents. The latter two groups are relatively common and more likely to come initially to the attention of the internist than to the neurologist.

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The hereditary metabolic myopathies are of special interest because they reveal certain aspects of the complex chemistry of muscle fibers. Indeed, each year brings to light some new genetically determined enzymopathy of muscle. As a consequence, a number of diseases formerly classified as dystrophic or degenerative have been added to the enlarging list of metabolic myopathies. There are now so many of them that only the most representative can be presented in a textbook of neurology. Complete accounts of this subject can be found in the section on metabolic disorders in Engel and Franzini-Armstrong and in DiMauro and colleagues (1992).

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The chemical energy for muscle contraction is provided by the hydrolysis of adenosine triphosphate (ATP) to adenosine diphosphate (ADP); ATP is restored by phosphocreatine and ADP acting in combination. These reactions are particularly important during brief, high-intensity exercise. During periods of prolonged muscle activity, rephosphorylation requires the availability of carbohydrates, fatty acids, and ketones, which are catabolized in mitochondria. Glycogen is the main sarcoplasmic source of carbohydrate, but blood glucose also moves freely in and out of muscle cells as needed during sustained exercise. The fatty acids in the blood, derived mainly from adipose tissue and intracellular lipid stores, constitute the other major source of energy. Carbohydrate is metabolized during aerobic and anaerobic phases of metabolism; the fatty acids are metabolized only aerobically.

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Resting muscle derives approximately 70 percent of its energy from the oxidation of long-chain fatty acids. As stated earlier, the circumstances during exercise are somewhat different. During a short period of intense exercise, the muscle uses carbohydrate derived from glycogen stores; myophosphorylase is the enzyme that initiates the metabolism of glycogen. With longer aerobic exercise, blood flow to muscle and the availability of glucose and fatty acids is increased. At first, glucose is the main source of energy during exercise; later, with exhaustion of glycogen stores, energy is provided by oxidation of fatty acids. Thus, muscle failure at a certain phase of exercise is predictive of the type of energy failure. A rising blood concentration of β-hydroxybutyrate reflects the increasing oxidation of fatty acids, and an increase in blood lactate reflects the anaerobic metabolism of glucose. The cytochrome oxidative mechanisms are essential in both aerobic and anaerobic muscle metabolism; these mechanisms are considered in Chap. 37 in relation to the mitochondrial diseases in which muscle tissue is prominently involved, and they are referred to here only ...

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