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.