124 1. lODOACETATE AND lODOACETAMIDE 



fore the iodoacetate is added, respiration is inhibited sooner and much 

 more completely. 



(c) Protection of 3-PGDH by S-ph as pJioglycer aldehyde. The steady-state 

 level of 3-phosphoglyceraldehyde may be higher under aerobic conditions 

 than under anaerobic conditions, as shown in yeast by Holzer and Holzer 

 (1953). Inch^cd, they found some protection aerobically. It is unlikely that 

 this is a major factor in most cases. 



(d) Alteration of the SH/SS ratio. Inasmuch as iodoacetate reacts only 

 with SH groups and not with disulfide groups, Turner (1937) postulated 

 that the SH/S8 ratio may be lower aerobically than anacrobically, a greater 

 fraction of the tSH groups being unavailable for reaction, and showed that 

 even small amounts of oxygen reduce the rate of inhibition of fermentation. 



(e) Deviation of pyruvate metabolism. The pyruvate formed from the EM 

 pathway normally may be oxidized through the cycle or reduced to lactate. 

 Heald (1953) believed that iodoacetate might inhibit the latter more strong- 

 ly because it also involves the utilization of NADH formed in the 3-PGDH 

 reaction. As pyruvate formation is reduced, less goes to lactate but essen- 

 tially as much into the cycle (see page 107). This applies, of course, to 

 aerobic glycolysis only. 



(f) Secondary interference with glucose phosphorylation. This has been suf- 

 ficiently discussed (see i)age 74). Anacrobically the ATP level may be low- 

 er and fall more rapidly than aerobically, and thtis the hcxokinase reaction 

 is depressed sooner under anaerobic conditions. Indeed, the inhibition of 

 anaerobic glycolysis is a vicious circle, in that depression of 3-PGDH re- 

 duces the ATP, which slows glucose phosphorylation, further reducing the 

 amount of 3-phosphoglyceraldehyde available for oxidation. 



(g) Presence of alternate pathways for carbohydrate oxidation. Oxidative 

 pathways for hexose utilization not involving an iodoacetate-sensitive step 

 may account for part of the uninhibited respiration. These will be discussed 

 in the following section. 



Any one or a combination of these may account for the differential ac- 

 tions reported and the actual explanation in a particular instance must 

 depend on ex])erimental evidence. Most of the hypotheses have had very 

 little or no experimental basis. On the basis of what evidence is available, 

 one would conclude that explanations (a), (b), (f), and (g) are the most 

 generally applicable. Those who believed fermentation and respiration to 

 be entirely distinct (e.g., Cayrol and Genevois, 1931) and those who be- 

 lieved them inseparable (e.g., Ehrenfest, 1932) were in general both wrong, 

 since in most cells respiration is to some degree dependent on the glycolytic 

 breakdown of carbohydrate through the EM pathway, but is seldom either 

 independent or completely dependent. 



