Iodoacetate inhibition of glyceraldehyde-3-phosphate dehydrogenase as a model of human myophosphorylase deficiency (McArdle's disease) and phosphofructokinase deficiency (Tarui's disease).
A model of the human neuromuscular disorders myophosphorylase deficiency and phosphofructokinase deficiency has been developed using intra-aortic injection of sodium iodoacetate in adult male rats. Iodoacetate selectively inhibits in vivo the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase. The iodoacetate-injected rats develop electrically silent cramps in leg musculature during ischemic (or vigorous non-ischemic) exercise. Post-exercise rhabdomyolysis is evidenced by a 10-fold serum CPK elevation, excessive uptake of 99mTc-diphosphonate by cramped muscle, and type IIB fiber damage (histochemically-demonstrated) in cramped muscle. Further analysis of this model will allow a greater understanding of the clinical syndrome associated with the human disorders and permit development of successful treatment programs.
D000818:Animals; D004195:Disease Models, Animal; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors*; D006008:Glycogen Storage Disease / Q000201:enzymology*; D006012:Glycogen Storage Disease Type V / Q000201:enzymology*; D007461:Iodoacetates / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009120:Muscle Cramp / Q000201:enzymology; D009132:Muscles / Q000201:enzymology; D010732:Phosphofructokinase-1 / Q000172:deficiency*; D005082:Physical Exertion; D051381:Rats
D007461:Iodoacetates; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010732:Phosphofructokinase-1