874 7. MERCURIALS 



around 0.002 mM, and completely by 0.01 mM. The ADP^s-ATP and 

 ADP-C^*-ATP exchanges are also inhibited, but perhaps not as strongly 

 (Wadkins and Lehninger, 1958; Chiga and Plant, 1959; Kahn and Jagen- 

 dorf, 1961). These exchange reactions are related intimately with oxi- 

 dative phosphorylation. Indeed, Wadkins and Lehninger (1958) postulated 

 that the Pj-ATP exchange is a measure of the two terminal reactions in 

 oxidative phosphorylation: 



Carrier — ^ X + Pi ^ carrier + P ^ — ^ X 

 P — X 4- ADP ±5 ATP + X 



where X is perhaps the enzyme protein, while the ADP- ATP exchange 

 measures only the last reaction. They further suggest that the mercurials 

 inhibit this last reaction principally, whereas 2,4-dinitrophenol acts on the 

 penultimate step. If the mercurials act solely on the transfer of phosphate 

 to ATP they would be good uncouplers, but actions elsewhere in the elec- 

 tron transport chain limit their efficiency. It is interesting that Griffiths 

 and Chaplain (1962) have found evidence for a new phosphorylated deriva- 

 tive of NAD following incubation of heart mitochondria with succinate 

 and P(^2. ATP can be formed from the intermediate and this reaction is 

 completely blocked by p-MB at 0.01 mM. This observation is compatible 

 with the scheme of Wadkins and Lehninger. 



FERMENTATION AND GLYCOLYSIS 



The first impression from surveying the studies of mercurial action on 

 fermentation and glycolysis is that these pathways are often surprisingly 

 insensitive to this group of inhibitors. In many cases it requires concentra- 

 tions greater than 1 mM to depress glycolysis significantly in cellular sys- 

 tems. Reference to Table 7-13 shows that several enzymes in the Embden- 

 Meyerhof pathway are quite readily inhibited by mercurials, e.g., hexo- 

 kinase, aldolase, 3-phosphoglyceraldehyde dehydrogenase, enolase, and lac- 

 tate dehydrogenase, concentrations of 0.001-0.05 mM usually inhibiting 

 50% or more in muscle, although little is known about the sensitivities of 

 the yeast enzymes. Since several enzymes in the pathway are susceptible, 

 one might anticipate that the sequential inhibition by mercurials at con- 

 centrations above 0.05 mM would produce a very strong over-all depression 

 of anaerobic COg or lactate formation. Three explanations for the failure to 

 do so are immediately apparent: (1) The mercurials do not penetrate into 

 the cells readily; (2) the glycolytic enzymes are protected in the cell (e.g., 

 by substrates or coenzymes); and (3) the large amount of nonenzymic ma- 

 terial in cellular preparations binds much of the mercurial. Cleland (1949) 

 found that 1 mM PM inhibits glycolysis in oyster eggs only 17% at 0-45 

 min and 48% at 45-90 min, whereas glycolysis in egg homogenate (with 



