884 7. MERCUEIALS 



is increased. There has been no study of the mechanism whereby such stim- 

 ulation is produced. One might postulate that the mercurials can increase 

 membrane permeability so that substrates can enter cells more rapidly, but 

 although this may be a factor it is clear that endogenous respiration can be 

 stimulated, as in the work of Shacter. It is also known that subcellular 

 preparations, and indeed certain enzymes themselves, are stimulated (page 

 815), so that one cannot expect to provide a comprehensive theory based 

 only on cell and tissue responses. Shacter felt that the mercurials might 

 react with certain thiols which regulate metabolism, but despite all the 

 discussion of such regulators in the past, there seems to be little evidence 

 at present for their importance. Of the several mechanisms suggested pre- 

 viously (page 1-453), one is at a loss to select any that would apply partic- 

 ularly to the mercurials. Since mercurials have been shown to reduce the 

 P : ratio in various isolated systems, it is possible that in the cell an un- 

 coupling action might increase Og uptake in a certain limited range of con- 

 centration, and it is also possible that the mercurials by a membrane effect 

 might alter ion movements and concentrations, thus secondarily bringing 

 about metabolic stimulation, but there is no direct evidence for either of 

 these mechanisms. Intracellular changes are undoubtedly so complex that 

 metabolic effects usually defy analysis. Consider the situation described by 

 Estler et al. (1960) in yeast treated with Hg++ (Fig. 7-34), the levels of all 

 the adenine nucleotides increasing at 0.2 mM, although Og uptake is scarcely 

 affected, while at higher concentrations the nucleotides change in a com- 

 plicated fashion and respiration is severely depressed. Unfortunately stim- 

 ulation was not recorded here, but it is only by thorough studies of this 

 type that one can hope to penetrate into the mysteries of inhibitor stim- 

 ulation. 



Although Meier (1926) reported that aerobic fermentation in yeast is 

 more potently inhibited than respiration by Hg++ — at 0.009 mM the 

 former was inhibited 72% and the latter not at all — subsequent work on 

 a variety of cells has indicated no general relationship between the sensi- 

 tivities of glycolysis and respiration, and even in yeast Weitzel and Bud- 

 decke (1959) found both to be inhibited similarly, at least at high concentra- 

 tion (1 mM) of Hg++. The respiration of oyster eggs is inhibited more than 

 glycolysis by PM (Cleland, 1949), whereas in oyster spermatozoa the res- 

 piration is inhibited by PM when glycolysis as measured by lactate for- 

 mation is increased (Humphrey, 1950). The utilization of pyruvate in these 

 cells may be more sensitive to mercurials than the glycolytic pathway. 

 Certainly the inhibition of respiration does not imply a reduction in glu- 

 cose uptake: In diaphragm, 1 mM p-MB depresses Og uptake 15%, lowers 

 the glycogen content, and yet increases glucose utilization somewhat (Haft 

 and Mirsky, 1952). In most cases (e.g., yeast and Chlorella), glucose respira- 

 tion is more sensitive than endogenous respiration to mercurials, but this 



