136 1. lODOACETATE AND lODOACETAMIDE 



lactose in mammary gland (Grant, 1936); sucrose in pea seeds (Turner, 

 1957); and cellulose in Acetohacter xylinum (Schramm et al., 1957). I know 

 of no case in which carbohydrate synthesis is increased by iodoacetate; this 

 is perhaps related, in part, to the fall in ATP associated with the action of 

 iodoacetate. 



What effect will iodoacetate have on the total uptake or utilization of 

 glucose? Since the factors involved here are many and complex it is dif- 

 ficult to predict the over-all result. Most cells probably do not have high 

 intracellular levels of free glucose and the level would be expected to rise 

 after addition of iodoacetate, particularly in those cells not possessing an 

 active pentose-P pathway. This occurs very markedly in rabbit erythro- 

 cytes, the glucose concentration rising from 16 mg% to 392 mg% in 5 hr in 

 the presence of 1 mM iodoacetate (Laris, 1958). We have noted that glucose 

 accumulation occurs in yeast treated with iodoacetate, concentrations as 

 high as 40-55 mM in the cell water being reached (Cirillo, 1962). These 

 cells were incubated with external glucose, but if the tissues are bathed in 

 glucose-free media the effect of iodoacetate is often to accelerate the loss 

 of glucose from the cells. For example, in pea stems the initial glucose is 

 1.12%, after incubation for 24 hr with auxin is 0.86%, and in the presence 

 of auxin and 0.6 mM iodoacetate is 0.64% (Christiansen et al., 1949); in 

 perfused frog liver, iodoacetate at 0.3-2 mM doubles the glucose output, 

 this presumably being mainly from glycogen breakdown and indicating less 

 utilization (Craig, 1959). The uptake and oxidation of glucose in adipose 

 tissue are accelerated by insulin. Iodoacetate concentrations having no ef- 

 fect on glucose oxidation directly inhibit the stimulation produced by in- 

 sulin (Mirsky and Perisutti, 1962). The binding of insulin to the tissue is 

 not prevented, so one must assume that an iodoacetate-sensitive uptake 

 mechanism is initiated by insulin. Human leucocytes accumulate galactose 

 to intracellular concentrations 3-6 times the external, and convert the ga- 

 lactose to galactose-1-P, UDP-galactose, and other products. Iodoacetate 

 at 1 mM increases the total radioactivity and the labeled galactose and ga- 

 lactose-1-P in the cells, when the leucocytes are incubated with galactose- 

 C^^ (Kalant and Schucher, 1963). This might be explained by a block of 

 the metabolism of galactose-1-P or, more tenuously, by assuming that gly- 

 colysis inhibits the transport of galactose so that depressed glycolysis would 

 accelerate galactose uptake. Hexose uptake is a complex phenomenon con- 

 trolled by many factors and the effects of iodoacetate have not yet been 

 clearly delineated. 



We shall now consider direct experiments on glucose uptake; some re- 

 sults are given in Table 1-22. It is seen that glucose uptake is almost uni- 

 formly inhibited, although not to the same extent as glycolysis in most 

 cases. The stimulation of glucose uptake by yeast at 0.1 mM iodoacetate 

 is interesting and is accompanied by a comparable stimulation of respira- 



