240 LIFE: ITS NATURE AND ORIGIN 



of the enzyme. Drugs like urethane, alcohol, ether, and similar 

 "lipoid solubles" seem to combine with bonds of the protein 

 carrier, when reversible denaturization by heat or pressure renders 

 these bonds available. 50 



Professor Clifford S. Leonard of the University of Vermont, in 

 discussing the problem of the role of sulfhydryl enzymes in the 

 mechanism of the action of certain chemotherapeutic agents 51 

 suggests that the action of mercurials and arsenicals is on protein 

 enzymes containing SH groups. To be useful, the drug must 

 adversely affect the catalysts of the invading organism, without 

 too much harm to the host; so research now includes work on the 

 biocatalysts of malarial plasmodia, trypanosomes, etc. According 

 to von Brand et a/. 52 90 per cent of the respiration of the South 

 American Trypanosoma crazii, in cultures, is stopped by inhibitors 

 of oxidases and dehydrogenases, and only 10 per cent by inhibitors 

 of SH enzymes. The respiratory mechanism of this organism is 

 therefore quite different from that of the African trypanosomes, 

 and Chagras disease, which it causes, does not respond to drugs 

 successfully used in the African type infections. 



Referring to the work of Professor E. A. G. Barron of the University 

 of Chicago and P. Singer, 52a which aimed to determine "which of the 

 enzymes are 'SH' enzymes and which enzymes are not dependent on 

 the presence of free SH groups for their activity," Professor Leonard 

 states: 



"We can perhaps review Barron and Singer's work to advantage 

 from a viewpoint which they did not discuss, namely the mechanism 

 of action of arsenicals and mercurials on parasites, and on the host's 

 tissues. For the concept that the essential attack of these agents is on 

 an essential enzyme system which is dependent on SH groups for its 

 function, or on multiple such systems, seems far more illuminating 

 than the general attack on proteins or on glutathione. RSH becomes 

 ESH, where E is the residual part of an enzyme. It would seem that 

 far lower concentrations than those needed for such general attack 

 would suffice to stop the intermediary metabolism of cells by means of 

 this inhibition of enzymes. What processes would thus be stopped? 

 Barron and Singer show that there are many SH enzymes. 



"Thus in the first phase of metabolism of carbohydrate, SH enzymes 

 include: muscle phosphorylase, phosphoglucomutase, hexokinases, and 

 phosphoglycaraldehyde oxidase. In the stages: pyruvate to lactate, or 

 to acetaldehyde and C0 2 , carboxylase is an SH enzyme, lactic oxidase 

 is not. In the oxidative phase of carbohydrate metabolism among 

 the SH enzymes are: hexosemonophosphate oxidase, pyruvic oxidase 



