Disorders of lipid metabolism in muscle.
At rest and during sustained exercise, lipids are the main source of energy for muscle. Free fatty acids become available to muscle from plasma free fatty acids and triglycerides, and from intracellular triglycride lipid droplets. Transport of long-chain fatty acyl groups into the mitochondria requires esterification and de-esterification with carnitine by the "twin" enzymes carnitine palmityltransferase (CPT) I and II, bound to the outer and inner faces of the inner mitochondrial membrane. Carnitine deficiency occurs in two clinical syndromes. (1) In the myopathic form, there is weakness; muscle biopsy shows excessive accumulation of lipid droplets; and the carnitine concentration is markedly decreased in muscle but normal in plasma. (2) In the systemic form, there are weakness and recurrent episodes of hepatic encephalopathy; muscle biopsy shows lipid storage; and the carnitine concentration is decreased in muscle, liver, and plasma. The etiology of carnitine deficiency is not known in either the myopathic or the systemic form, but administration of carnitine or corticosteroids has been beneficial in some patients. "Secondary" carnitine deficiency may occur in patients with malnutrition, liver disease, chronic hemodialysis, and, possibly, mitochondrial disorders. CPT deficiency causes recurrent myoglobinuria, usually precipitated by prolonged exercise or fasting. Muscle biopsy may be normal or show varying degrees of lipid storage. Genetic transmission is probably autosomal recessive, but the great male predominance (20/21) remains unexplained. In many cases, lipid storage myopathy is not accompanied by carnitine or CPT deficiency, and the biochemical error remains to be identified.
D000214:Acyl Coenzyme A / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D002331:Carnitine / Q000172:deficiency / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency / Q000378:metabolism; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000201:enzymology*; D009132:Muscles / Q000201:enzymology; D009135:Muscular Diseases / Q000201:enzymology*; D005082:Physical Exertion
D000214:Acyl Coenzyme A; D005230:Fatty Acids, Nonesterified; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine