The role of lipid peroxidation in McArdle's disease: applications for treatment of other myopathies.
Experimental therapies for McArdle's disease have been directed toward increasing substrate availability to exercising muscle. Such therapies to date have proven largely unsuccessful. These include administration of isoproterenol to increase blood flow, glucagon treatment to elevate serum glucose and increased dietary fat intake. Each of these therapies also results in greater levels of unesterified fatty acids in blood. More recently, a high protein diet is suggested to provide increased amounts of amino acids which would be available as fuel sources. We hypothesize that the absence of myophosphorylase in McArdle's disease creates an imbalance between the enzymes of the redox systems that control the generation, propagation and inactivation of free radicals. This occurs because muscle cells are forced to rely more heavily on fatty acid oxidation. The resulting free radical damage to cellular components disrupts metabolic control and increases the permeability of membranes. Elevated levels of Ca2+ in the sarcoplasm activate proteases, phospholipases and other catabolic enzymes initiating muscle fatigue and cramping. Lipid peroxidation is a consequence of normal muscle activity and may occur unchecked in individuals with McArdle's disease. Continued muscle activity in the absence of a favorable nutritional environment may promote the progression of the disease by increasing susceptibility to oxidative stress.
Russo
P J
PJ
University of Health Sciences, College of Osteopathic Medicine, Department of Biochemistry, Kansas City, Missouri 64124.
Phillips
J W
JW
Seidler
N W
NW
D000975:Antioxidants / Q000494:pharmacology; D004032:Diet; D015444:Exercise / Q000502:physiology; D006012:Glycogen Storage Disease Type V / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008954:Models, Biological; D009132:Muscles / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction
D000975:Antioxidants