450 CHEMICAL DYNAMICS 



also, that the loss of proteolytic activity which occurs on heating 

 solutions of proteolytic ferments is to be attributed, not to auto- 

 hydrolysis of the ferment, but to the partial or complete conversion 

 of the hydrolysing enzyme into the synthesizing form. From the 

 above account of the chemical mechanics of the enzymatic hydroly- 

 sis and synthesis of proteins it would appear that the "inactiva- 

 tion" of proteolytic ferments by heat (provided actual coagulation 

 does not occur) should be a reversible process, if not in the pure 

 enzyme-solution, at any rate in the presence of products of protein 

 hydrolysis.* Owing to the fact that the enzymatic activity of 

 hydrolysing enzymes has in the past been identified with their 

 power to accelerate hydrolysis, the application of heat to enzyme 

 solutions has always been regarded as involving the "destruction" 

 of the enzymes and restoration of their activity under varying 

 conditions following a return to lower temperatures has not been 

 anticipated and therefore has not been looked for with any especial 

 care. Nevertheless, Bayliss (4) has observed that the power of 

 heated trypsin to accelerate protein hydrolysis is to some extent 

 regained after the heated enzyme has been mixed with protein for 

 some time, and Howell (33) has observed that thrombin is not 

 "destroyed" by moderate heating, but is reversihly thermolabile 

 inasmuch as it regains its activity on treatment with alkali and 

 subsequent neutralization at lower temperatures. Gramenisky 

 (21) has also observed that oxidase inactivated by heating rapidly 

 regains its activity on standing at lower temperatures. f 



6. The Thermodynamics of the Enzymatic Hydrolysis and 

 Synthesis of Proteins. — The thermodynamical aspect of the 

 hypothesis developed above is of interest. As I have pointed out, 

 the shift in equilibrium of the system protein ^ products towards 



digesting group of the ferment while the "haptophore" group, by which the 

 enzyme attaches itself to the protein molecule, is unaffected. The heated 

 ferment he terms "zymoid," and he believes that the initial decrease in the 

 conductivity of mixtures of casein and heated ferment is to be attributed to 

 the formation of a compound between the "zymoid" and the protein. This 

 view, of course, fails to account for the reversion of protein hydrolysis which 

 is brought about by heated pepsin. 



* Since, as we have seen in the preceding section, these will catalyse the 

 reaction FF + H2O -^ HFFOH. 



t In this connection it is of extreme significance that the oxidase employed 

 by Gramenisky behaved, at 80 degrees, no longer as an oxidase but as a reduc- 

 tase, or reducing ferment. 



