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
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).
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.
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 ...