204 IMMUNO-CATALYSIS 



2. Identity of the Nature of the Inhibition of Enzymes by 

 Homologous Antibodies with Antigen-Antibody Reactions 



A consideration of the results of various studies on the specific side 

 groupings of proteins in relation to their various biological activities 

 fails to establish a direct causal relationship. It is true that modifica- 

 tions in certain groups result in reversible inactivations, but what other 

 changes underlie such modifications are not known. It must be remem- 

 bered that the integrity of the whole protein molecules to which 

 various side groups are attached, and not the groups by themselves, 

 determines the complex mechanism of the biological activities of pro- 

 teins. For example, the relation of the SH groups in succinoxidase 

 does not bear even a suggestion of similarity to their role in the activa- 

 tion of papain or the activity of pneumococcal hemolysin. We do not 

 know as yet what particular configuration or groupings in one protein 

 enable the heme group to function as cytochrome oxidase, and in 

 another protein enables it to act as a catalase, or cytochrome c. What 

 makes a certain protein to enable pyridine-adenine-dinucleotide to 

 function as coenzyme for lactic acid dehydrogenase and another protein 

 enables it to act as coenzyme for phosphoglyceraldehyde dehydrog- 

 enase? 



Similar difficulties arise when we consider the groupings involved 

 in the combinations between antigens and antibody. There is no doubt 

 that certain specific groupings in these reactants make them mutually 

 attractive and a union takes place. The suggestion of Heidelberger and 

 Kendall (1929), and the experimental data provided by the studies 

 of Chow and Goebel (1935), and Goebel and Hotchkiss (1937), as 

 we have discussed elsewhere, contribute to the support of the idea that 

 the positively charged -NHs groups in antibodies and the negatively 

 charged -COOH groups in antigens might be involved in the com- 

 binations between antigens and antibodies. According to Pauling 

 (1945) hydrogen bond linkages may arise from reactions involving 

 positively charged imino, =NH, and negatively charged carboxyl, 

 -COO~, groups forming R-N-H .... O-CO-R bonding. It is sug- 

 gested that the forces of these bondings play a role in keeping the 

 proteins in their specific configurations. From the results of haptenic 

 inhibitions of antigen and antibody reactions, it has been suggested 

 (Pressman, Bryden and Pauling, 1948) that the principal forces of 



