2,6 JOHN H. NORTHROP 



of the reaction so that a slightly different enzyme is formed as well as 

 the usual enzyme. When the new substrate is no longer present the re- 

 action returns to its normal course and the normal enzyme alone is 

 formed. Examples of similar reactions in which the course of an enzyme 

 reaction is affected by the presence of substances other than enzyme and 

 substrate are well known. Thus either trypsin or an inert protein may 

 be formed during the autocatalytic formation of trypsin from trypsino- 

 gen; the nature of the product depends on the />H of the solution 

 (Kunitz, 1939a). Different tyrosinases may be formed from protyrosi- 

 nase under different conditions (Bodine, 1945). Abderhalden and 

 Ehrenwall (1933) found that addition of certain peptides caused glycyl- 

 leucine to be hydrolyzed by trypsin, whereas the reaction did not occur 

 when trypsin and glycyl-leucine alone were present. The experiments 

 were extended by Bergmann and his collaborators (cf. page 11). The 

 added peptides appear to act as co-enzymes. 



The specificity of the amino acid oxidases is completel}^ changed by 

 the addition of other proteins or amino acids to the reaction mixture 

 (Edlbacher, 1946). 



The products of an enzyme reaction usually combine with the enzyme 

 so that the fact that a reaction occurs between the enzyme produced and 

 the substance which caused its production does not differ qualitatively 

 from many enzyme reactions. The distinguishing factor in the present 

 case is that one of the products of the reaction is itself an enzyme. 



V. Formation of Antibodies 



Antibodies are considered to be modified serum globulins which are 

 changed in such a way as to react with the homologous antigen (cf. 

 Marrack, 1938; Zinsser, Enders, and Fothergill, 1939; Burnet, Free- 

 man, Jackson, and Lush, 1941 ; Landsteiner, 1945; and Sevag, 1945). 

 There is no doubt that antibodies are proteins, but their relationship 

 to the serum globulins appears to be somewhat uncertain owing to the 

 fact that neither antibodies nor serum globulins have been obtained in 

 pure form (cf. Roche, Derrien, and Mandel, 1944a and 1944b). ^^ Any 



11 Crystalline diphtheria antitoxin (Northrop, 1941) is probably a pure protein and 

 is not a globulin, although it cannot be separated from the globulin fraction if mixed 

 with it by any known procedure except precipitation with the homologous antigen. 

 This result would prove that antibodies are distinct chemically and immunologically 

 from the normal serum proteins, were it not for the fact that the toxin-antitoxin complex 

 used to prepare the crystalline antibody was digested with trypsin. It is possible to 

 assume, therefore, that the pure crystalline antibody does not represent the natural 

 antibody but is an hydrolysis product. 



Antibodies are reported to be associated with different serum proteins in different 



