J. S. FRUTON 



of the enzyme-substrate complex — the reacting nucleus — while the 

 rest of the complex may be expected to have some influence only on 

 the rate of the enzymic action . Two homospecific enzymes thus may 

 differ in many respects but are assumed to contain identical essential 

 centers, and therefore yield, with the same substrate, two enzyme- 

 substrate compounds containing identical reacting nuclei. 



■ Support for this hypothesis comes from the finding that, if each 

 of two homospecific enzymes is allowed to act on two substrates, the 

 quotient of the rates of hydrolysis of each substrate by the two enzymes 

 is independent of the nature of the substrate. For example, papain 

 trypsinase was found to hydrolyze benzoylargininamide with a proteo- 

 lytic coefficient* of 167, while beef spleen trypsinase splits the same 

 substrate with a coefficient of 8.3. The quotient of these two values is 

 20.1. If the same enzymes are tested with benzoyllysinamide as the 

 substrate, 78 and 3.8 are the coefficients found, giving a quotient of 

 20.5. Similar examples may be cited for other pairs of homospecific 

 enzymes; for further data, cj. Bergmann (6). The fact that two homo- 

 specific enzymes, Ei and Eo, give similar proteolytic quotients for the 

 hydrolysis of the substrates Si and S2, may be explained by the assump- 

 tion that the enzyme substrate compounds, EiSi, E2S1, E1S2, and 

 E2S>, all contain identical reacting nuclei. 



Furthermore, if this concept is correct, it may be expected that 

 parts of the enzyme molecule may be split off" without destruction of 

 the enzymic activity, and without alteration of the enzymic specificity. 

 Indeed, Kunitz (21) has shown that a-chymotrypsin may be trans- 

 formed into 7-chymotrypsin, and that in the course of this transforma- 

 tion about one-third of the a-chymotrypsin molecule is removed. 

 However, neither the proteolytic activity toward proteins nor the 

 specificity of action on synthetic substrates was altered. 



It may be added that both a- and 7-chymotrypsin have been 

 found to exhibit two distinct proteolytic specificities, one of the amino- 

 peptidase type and another of the proteinase (endopeptidase) type 

 (18). Since all efforts to alter the ratio of the two specificities were 

 unsuccessful, and also since a- and 7-chymotrypsin both conform to the 



* The proteolytic coefficient (C) is defined as the value of the reaction 

 velocity constant (A") for the hydrolysis of a peptide bond in the presence of an 

 amount of enzyme corresponding to one milligram of protein nitrogen per cubic 

 centimeter of the test solution. 



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