876 7. MERCURIALS 



Gemmill and Hellerman (1937) found that Hg++, p-MB, and PM all block 

 glycolysis in extracts of frog muscle, but the concentrations used were too 

 high and usually unspecified. Separated fibers of cockroach muscle treated 

 with 1 mikf p-MB show no change of COg formation and a rather marked 

 increase in lactate formation if only glucose is added, but in the presence 

 of glucose + ATP, COg production is inhibited 67% and there is no effect 

 on lactate (Barron and Tahmisian, 1948). This behavior is quite different 

 from that of iodoacetate, which inhibits only in the absence of added ATP. 

 The authors felt that the failure to depress lactate formation in any case 

 is perhaps a characteristic of invertebrate muscle, since Harting (1947) had 

 observed 1 mM p-MB to produce only stimulation of glycolysis in strips of 

 scallop and thyone muscle. However, Krueger (1950) has shown that 2 min 

 perfusion of frog muscle with 37 mM Hg++ essentially doubles the lactate 

 formation. The only serious study of muscle glycolysis was done by Bailey 

 and Marsh (1952) on rabbit psoas homogenates. Here p-MB produces def- 

 inite inhibition (see accompanying tabulation), but the concentration is so 



high that it is remarkable that the inhibition is not much greater. It was 

 believed that aldolase inhibition is responsible for the results but from the 

 data it is not possible to localize the site of action so closely. The authors 

 pointed out that 3-phosphoglyceraldehyde dehydrogenase is not so readily 

 inhibited by p-MB as by iodoacetate. The transfer of phosphate from crea- 

 tine-P to ADP is immediately and completely blocked by p-MB, so that 

 creatine-P remains at its initial level, and this must also be a factor in the 

 inhibition, since it would prevent regeneration of ATP. It is thus impossible 

 in this study to determine what effects p-MB might have directly on the 

 Embden-Meyerhof pathway. All of the results on intact muscle tissue seem 

 to be incompatible with the demonstration by Demis and Rothstein (1955) 

 that glucose uptake by diaphragm is very sensitive to Hg++, being almost 

 completely inhibited by 0.2 mM. However, respiration and anaerobic lac- 

 tate formation, being dependent on endogenous substrate, are much less 

 sensitive and are only slowly inhibited. This will be considered in greater 

 detail when the effects of mercurials on respiration are discussed (page 884). 



