Iodoacetate inhibition of glyceraldehyde-3-phosphate dehydrogenase as a model of human myophosphorylase deficiency (McArdle's disease) and phosphofructokinase deficiency (Tarui's disease).

Abstract

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.

• Authors: R A Brumback
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 48 Issue 3 Pg. 383-98 (Dec 1980) ISSN: 0022-510X [Print] Netherlands
• PMID: 6449564 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Iodoacetates
• Glyceraldehyde-3-Phosphate Dehydrogenases
• Phosphofructokinase-1

Topics

• Animals
• Disease Models, Animal
• Glyceraldehyde-3-Phosphate Dehydrogenases (antagonists & inhibitors)
• Glycogen Storage Disease (enzymology)
• Glycogen Storage Disease Type V (enzymology)
• Iodoacetates (pharmacology)
• Male
• Muscle Contraction (drug effects)
• Muscle Cramp (enzymology)
• Muscles (enzymology)
• Phosphofructokinase-1 (deficiency)
• Physical Exertion
• Rats