REACTIONS WITH PROTEINS 751 



administration prevents mercurial poisoning in mice, and that it reduces 

 the inhibition of pyruvate oxidase by HgClg at high concentrations (Gru- 

 nert, 1960; Grunert and Rohdenburg, 1960). It is interesting that with 

 lower concentrations of HgCla (1.3 mM), lipoate increases the inhibition of 

 pyruvate oxidation in intact cells of Streptococcus faecalis, the mercaptide 

 possibly entering the cells more readily than the complexes of Hg++. It 

 would thus appear that mercurials react with coenzyme A and lipoate, 

 but how rapidly and how tightly are not known. 



Finally, we consider the problem of the splitting of thioesters by the 

 mercurials. Sachs (1921) showed that acetylthioethyl esters are rapidly 

 split by HgClg to acetate and mercurothioethanol, and in general all acyl 

 mercaptans seemed to behave in this way. Thus Lynen et al. (1951) in 

 their early studies on active acetate and coenzyme A investigated acetyl- 

 CoA and found it to be split by approximately 100 niM Hg acetate, a result 

 of questionable significance in physiological work. Stern (1956) studied ace- 

 toacetyl-CoA, a thioester of importance in lipid metabolism and possessing 

 a strong absorption maximum around 303 m//, and found that HgClg at 

 concentrations higher than 0.001 mM produces a rapid decrease in this 

 absorption, 0.1-0.2 mM completely abolishing it, this corresponding to 

 about a 1 : 1 molar ratio between Hg and thioester. The following reaction 

 sequence was suggested: 



Hg++ + AcAc— S— CoA- -> Hg— AcAc— S— CoA+ 

 Hg— AcAc— S— CoA+ + H2O -> Hg++ + AcAc" + HS— CoA 

 Hg++ + HS— CoA -> Hg— S— CoA+ + H+ 



The initial reaction is apparently with the enolate group of the acetoacetyl 

 radical. Stern believes that this reaction, occurring at such low concentra- 

 tions of Hg++ and so rapidly, may well be of great importance in the effects 

 of the mercurials on metabolism. However, Gibson et al. (1958) reported 

 that p-MB does not react with or split succinyl-CoA at a significant rate, 

 and Sanner and Pihl (1962) found a variety of thioesters to be resistant to 

 p-MB (e.g., acetyl-CoA, succinyl-CoA, and benzoyl-CoA). From this limited 

 work one might conclude that HgClj can split some thioesters but that ^^-MB 

 cannot. But Vagelos and Earl (1959) found that, in contrast to most thio- 

 esters, malonyl semialdehyde pantetheine reacts readily with p-MB, and 

 proposed that /5-carbonyl thioesters may be susceptible. The possible role 

 of these reactions in metabolic inhibitions is at present unknown. 



REACTIONS WITH PROTEINS 



It was believed in years past that mercury, in common with other heavy 

 metals, is adsorbed onto proteins, denaturing and precipitating them, but 

 recent work has shown that under appropriate conditions stoichiometric 



