886 7. MERCURIALS 



(Eltz and Vandemark, 1960). There are no data for comparing the relative 

 sensitivities of the Embden-Meyerhof and pentose-P pathways. 



As appears to have been the case with most of the workers who have 

 examined the effects of the mercurials on respiration, I find little to say 

 that seems worthwhile. The most interesting aspects of respiratory inhibi- 

 tion probably pertain to the metabolic basis of certain cellidar functions, 

 e.g., gastric secretion (page 914) or renal transport (page 917). The site of 

 action to inhibit respiration is unknown and multiple sites are likely. We 

 know little of the penetration of mercurials into cells and the intracellular 

 concentrations attained, and the information is lacking to evaluate the im- 

 portance of nonenzymic effects. These gaps in our knowledge apply not 

 only to respiration but essentially to all cellular activities. One can at least 

 state with fair certainty that the mercurials do not act like other SH re- 

 agents, such as iodoacetate or the arsenicals, i.e., their pattern of inhibition 

 is quite different. 



VARIOUS METABOLIC PATHWAYS 



In this section we shall consider briefly some of the important types of 

 metabolism which are readily inhibited by the mercurials. Only the more 

 interesting aspects and interpretable investigations will be mentioned. The 

 effects of the mercurials on metabolism are complex and vague in all cases, 

 so it is essential to emphasize those studies in which clear-cut results have 

 been obtained, even though the work is limited to only a certain phase of 

 the over-all pathway and the exact site or mechanism of action is unknown. 

 The few systems discussed will at least point out clearly the manifold potent 

 inhibitions which can be exerted by the mercurials and will serve to establish 

 the fact that specific effects on metabolism can seldom, if ever, be achieved 

 in cellular systems. Perhaps with the increasing knowledge of the detailed 

 actions of the mercurials, there will arise situations in which selective blocks 

 can be produced under controlled conditions, but at the present time there 

 is not much reason for optimism. 



Lipid Synthesis 



The long sequence of reactions in the biosynthesis of sterols seems to be 

 strongly inhibited by mercurials at different sites. The total incorporation 

 of mevalonate-C^* by Lactobacillus casei over 4 hr is inhibited 59% by 0.1 

 mif p-MB and 96% by 1 mM (Thorne and Kodicek, 1962). The conversion 

 of farnesyl-PP and mevalonate to squalene by various fractions of rat liver 

 is depressed 50% by p-MB, p-MPS, and Hg++ at concentrations near 0.05 

 mM, and essentially completely by concentrations much above 0.1 mM 

 (Popjak et al., 1958; Anderson et al., 1960; Goodman and Popjak, 1969). 

 The further conversion of squalene to sterols is 97% blocked by 0.33 mM 



