BIOGRAPHICAL MEMORANDA 



ed should carry precisely such a guarantee. This consideration led to 

 the successful experiments in which it was shown that a filtered zymase 

 residue, no longer capable of fermenting sugar, even when supple- 

 mented with hexose diphosphate and acetaldehyde, and hence co- 

 zymase free by the most rigorous standards, could be reactivated by 

 mixing it with a boiled aliquot of the same preparation. This result was 

 interpreted to mean that the boiled extract, in which the proteases 

 had been destroyed, contained protease-inhibiting materials. The al- 

 ternative explanation that a low-molecular weight substance needed 

 for fermentation, a true coenzyme as we now understand this term, 

 could be generated by boiling co-zymase-free zymase, was not con- 

 sidered; in view of the fact that nothing was yet known about the 

 nature and function of coenzymes this is not surprising. 



The conclusion of this extensive investigation was, therefore, that 

 the co-zymase effect could be attributed to one or more of the following 

 factors : 



i. an initial hydrogen acceptor function, such as exhibited by acetal- 

 dehyde ; 

 2. an activation of the phosphorylating principle by hexose diphos- 

 phate; and 

 j. protection of zymase against proteolytic degeneration. 

 Thus it appeared that the term co-zymase had actually been applied 

 to three entirely different types of substances, with different modes of 

 action. For this reason Kluyver and Struyk argued that it would be 

 best to 'banish the notion of a coenzyme altogether from the litera- 

 ture, and to replace it by the much more rational concept that a cell- 

 free fermentation requires, in addition to zymase and phosphatase, 

 the presence of an initial acceptor, of an hexose phosphate ester, and 

 of substances that can regulate the proteolysis of the zymase system. 

 . . . Although the function of the coenzyme had thus far remained 

 entirely obscure, it is now possible to indicate the nature of its activity, 

 and even to link it with phenomena whose importance for the cell-free 

 fermentation had long been recognized. . . . Further cogitations then 

 lead to the idea that the indispensability of the proteolysis-regulating 

 factors should be ascribed to the fact that, for its maintenance and for 

 the normal execution of its functions, the living cell requires the har- 

 monious cooperation of the principles it contains. If this harmony 

 is disrupted, as happens during the isolation of the zymase, and 



102 



