INHIBITION OF METABOLISM 721 



from the -flT^'s given by Singer and Hofstee (1948 b) shows that, for the 

 substrates used with o-iodosobenzoate, (S') varies from 4 to 23 at least and, 

 furthermore, the variation of the inhibition with (S') is as one would expect 

 from Eq. 6-1, i.e., it decreases with increasing (S'). Thus the results with 

 o-iodosobenzoate can be explained quite simply. However, it is not implied 

 that this will explain all of the results obtained by Singer, and it is quite 

 possible that with p-chloromercuribenzoate, where a bulky group is added 

 to the enzyme, steric factors also play a role. The purpose of the foregoing 

 treatment is to indicate the importance of keeping (S') constant when com- 

 paring inhibitions with different substrates. 



INHIBITION OF METABOLISM 



Very little quantitative work has been done on the effects of o-iodoso- 

 benzoate on glycolysis, respiration, the tricarboxylate cycle, or other me- 

 tabolic pathways, so that the following is not so informative as indicative 

 of possibly interesting experiments to be done. From Table 6-1 it is evident 

 that few glycolytic enzymes have been tested and these few are not particu- 

 larly sensitive to o-iodosobenzoate. Only one investigation of glycolysis 

 in vivo has apparently been reported, that of Harting (1947), who found 

 o-iodosobenzoate at 1 mM to stimulate scallop muscle anaerobic glycolysis, 

 as does p-chloromercuribenzoate. This may not be due to direct action on 

 the glycolytic system, but to some effect on the muscle membranes facilitat- 

 ing glucose entry. Glycolysis in muscle homogenates is definitely inhibited 

 by 4 milf o-iodosobenzoate (Bailey and Marsh, 1952). The changes in the 

 pH and phosphate fractions with time are modified, as shown in Table 6-2. 

 The fall in pH is quite strongly inhibited and the normal decrease in ATP 

 is accelerated, presumably by inhibiting ATP formation. The effects on 

 fructose- 1,6-diP are interesting; in the control there is an initial accumula- 

 tion followed by a fall to low levels — o-iodosobenzoate blocks the accu- 

 mulation partially, but what does accumulate remains, indicating some in- 

 hibition of aldolase or phosphoglyceraldehyde dehydrogenase. Part of the 

 depression of the early accumulation may be due to the low levels of ATP, 

 but it is likely that some inhibition is exerted on the enzymes forming fruc- 

 tose-l,6-diP, perhaps hexokinase. The prevention of the fall in creatine-P 

 is undoubtedly due to the potent inhibition of the transfer of the phosphate 

 to form ATP. The minor accumulation of phosphoglyceraldehyde produced 

 by o-iodosobenzoate may also point to some block of the dehydrogenase, 

 not unlikey at this rather high concentration. 



One might expect o-iodosobenzoate to inhibit respiration fairly strongly 

 since several dehydrogenases and cycle enzymes are quite sensitive. The 

 respiration of sea urchin spermatozoa is depressed almost completely by 

 0.3-1 milf o-iodosobenzoate, although lower concentrations around 0.1 txlM 



