CHAPTER 1 



lODOACETATE AND lODOACETAMIDE 



lodoacetate and related compounds have been used extensively for many 

 years to inhibit the metabolism of glucose and other carbohydrates to pyru- 

 vate aerobically, or to lactate, ethanol, and various fermentative products 

 anaerobically, and iodoacetate has often been considered to be a rather 

 specific inhibitor of glycolysis. Specific inhibitors of this pathway of me- 

 tabolism would be valuable for many studies attempting to evaluate the 

 role of glycolysis in cellular growth or function, and thus it is important 

 to establish as clearly as possible how well iodoacetate can achieve such 

 a selective effect and to determine the optimal conditions for its use. Iodo- 

 acetate has also been classified as an SH reagent by reason of its ability 

 to alkylate these groups and we must consider carefully if this is the sole, 

 or most important, reaction occurring under the usual experimental con- 

 ditions, lodoacetate has fallen into disfavor among certain enzymologists 

 because it frequently does not react as readily with enzyme SH groups as 

 do the mercurials and some other SH reagents. However, it is exactly this 

 behavior which makes iodoacetate a valuable tool in metabolic studies since 

 it allows a degree of selectivity to be exerted. The mercurials are without 

 question more reliable for the detection of enzyme SH groups but have 

 little value in work on the cellular level inasmuch as so many components, 

 both enzymic and nonenzymic, possess SH groups and react readily with 

 the mercurials. The emphasis in this chapter, therefore, will be placed on 

 the metabolic and functional aspects of iodoacetate action. 



HISTORICAL DEVELOPMENT 



The early development of the alkylating type of SH reagent involved 

 almost exclusively the use of bromoacetate. Steinauer (1874) in Berlin was 

 particularly interested in the actions of bromide and organic bromine com- 

 pounds (e.g., bromalhydrate and bromoform) and, while investigating these 

 substances, found that bromoacetate injected subcutaneously in frogs in 

 doses of 5-10 mg kills the animals in 2-3 hr, and that the animals suffer a 

 progressive respiratory and cardiac depression. He concluded that the car- 



