AEROBIC METABOLISM OF CARBOHYDRATE 111 



1935), although Kandler et al. (1961) found only inhibition, an unexplained 

 discrepancy. Barron and Goldinger (1941) found that 1 mM iodoacetate 

 markedly stimulates the respiration of sea urchin spermatozoa, and showed 

 that this is not due to a splitting of the iodoacetate into acetate and 

 iodine, since acetate does not stimulate the respiration and iodine only in- 

 hibits. The stimulation involves the whole respiration since the CO2 out- 

 put increases to the same degree, the R.Q. remaining constant. Barron et al. 

 (1948) postulated that the stimulation may be due to the reaction of iodo- 

 acetate with the soluble thiols of the cells, thereby removing a control of 

 respiration, whereas respiratory inhibition is due to reaction with the fixed 

 (or enzyme) SH groups. In most of the cases of stimulation the pH was 

 above 7, and for the sea urchin spermatozoa was 8.2. Possibly an initial 

 action on the membranes of the cells occurs, leading to permeability changes 

 and increased respiration. Another explanation may be related to the Crab- 

 tree effect (increased glucose depresses mitochondrial oxidations), in that 

 blocking of the EM pathway may temporarily stimulate the oxidation of 

 accumulated substrates through the cycle. 



Respiration in the Presence of Glucose 



One might expect that the inhibition of respiration in the presence of 

 glucose would be greater than that of endogenous respiration on the basis 

 that more of the O.2 uptake is dependent on the EM pathway. However, 

 this is not necessarily true. First, the presence of iodoacetate-resistant oxi- 

 dative pathways for glucose could allow glucose to be oxidized more readily 

 than the endogenous substrates. Second, the greater rate of oxidations in 

 the presence of glucose, even in the presence of iodoacetate, could maintain 

 a higher ATP level and hence phosphorylation of glucose would not fail as 

 rapidly as the endogenous respiration. Third, in certain tissues with high 

 aerobic glycolysis, such as HeLa cells, the addition of glucose aerobically 

 increases the lactate formation markedly but may even depress the respira- 

 tion. Here iodoacetate will inhibit glucose utilization and lactate produc- 

 tion, but the iodoacetate-resistant fraction of the respiration may remain 

 essentially the same, resulting in a smaller per cent inhibition of the respira- 

 tion in the presence of glucose. Some inhibitions of glucose respiration are 

 presented in Table 1-18 (others will be mentioned later). Where direct com- 

 parison of endogenous and glucose respiration can be made, one finds that 

 the latter may be inhibited more, the same, or less than the endogenous 

 respiration, which is actually what one should expect. The accompanying 

 tabulation shows examples of all three situations. In Ehrlich ascites tumor 

 cells, iodoacetate at 0.1 mM almost completely prevents the formation of 

 lactate, inhibits endogenous respiration 15%, but actually stimulates the 

 O2 uptake with glucose present due to the suppression of the Crabtree ef- 

 fect from 48% to 28% (Wenner and Cereijo-Santalo, 1962). 



