CHEMOTHERAPY 



far been undertaken but they suggest an answer. Normal washed 

 staphylococci are able to hydrolyze added adenosine triphosphate, and 

 glycerophosphate. Tyrocidine-trealed cells, which show a burst of 

 phosphatase activity toward their own small complement of phosphate 

 esters, are not able to operate any faster upon an adequate concentra- 

 tion of added phosphate esters than the normal cells did before their 

 membranes were made permeable. With certain limitations, these 

 experiments indicate that phosphatase and adenosinepyrophosphatase 

 are situated on or near the surface of these bacteria, and cytolytic 

 injury allows substrates from the interior of the cell to leak out into 

 the medium, where they can be hydrolyzed. It will be evident that 

 tyrocidine can possibly afford us a novel means of studying the workings 

 of the cell. 



We may stop to inquire whether there is not good reason why 

 phosphatases should be able to act at the periphery of the cell. Like 

 esterases, peptidases, amylases, etc., their function is probably always 

 to break dow^n complex substances since, like these other hydrolytic 

 enzymes, they appear unable to incorporate the energy needed for 

 the corresponding synthesis. Peripherally distributed phosphatases 

 may serve in part as agencies for converting phosphate esters, which 

 appear to be generally nondiffusible, into a form capable of entering the 

 cell. * Those cells able or obligated to use certain complex products 

 of other cells as nutrients must be prepared to degrade these extraneous 

 substrates to an acceptable form. In these cases we may expect other 

 hydrolytic enzymes such as those mentioned to be active, although 

 perhaps not entirely localized, at the cell boundary — more or less in 

 contrast with the enzymes of respiration, fermentation, and synthesis. 

 Many extracellular proteinases and polysaccharidases have been found 

 in the medium surrounding the cells which produce them. And re- 

 cently there have been interesting indications that the enzymes hy- 

 drolyzing trehalose (in yeasts) and lactose (in yeasts and colon bacilli) 



* This is not in conflict with the possibility that, after hydrolysis, some 

 substrates may be phosphorylated by the cell itself during absorption, as suggested 

 by Lundsgaard, Verzar and others for the case of glucose absorption from the 

 lumen of the kidney tubules or the intestine. The whole selective mechanism 

 would ensure that foreign, and perhaps inimical, substances would not g£un ad- 

 mission. 



