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 "Causes of metabolic myopathies" 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.
ENERGY SUBSTRATES IN EXERCISING 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 .
- 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 .
- 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").