212 IMMUNO-CATALYSIS 



ner, the immune inhibitions of the metaboHsm of the small molecular 

 weight substances cited below do not appear to be due to mechanical 

 obstructions resulting from or associated with antigen-antibody re- 

 actions. 



In other sections of the present treatise, the inhibition by homolo- 

 gous antibodies of various enzymes which specifically catalyze the 

 metabolism of pyruvate, penicilhn, tyrosine, luciferin, lecithin, urea, 

 sucrose, amygdalin, tributyrin lipids, and d-glyceraldehyde-3-phos- 

 phate will be described. These substances are small molecular weight 

 substances. Kirk and Sumner (1931) demonstrated that rabbits im- 

 munized against urease could survive 1000 lethal doses of urease. This 

 result shows that in the animal the system urease-anti-urease complex 

 is in an enzymatically inactive state, or that the wall set up by the 

 anti-urease molecules around the urease molecule is so tightly packed 

 that even an urea molecule of 60 molecular weight is incapable of 

 reaching the active site of the enzyme. As discussed above, a few mole- 

 cules of an antibody combined with an antigen molecule do not appear 

 to us to be capable of forming a solid wall impermeable to urea 

 molecules. 



Lipmann and his associates (Zamecnik, Brewster and Lipmann, 

 1947) have demonstrated that lecithinase of CI. welchii is completely 

 inhibited by homologous antibody. The reactions between the lecithin- 

 ase and antibody, and that of the enzyme and its substrate lecithin 

 are competitive. When the substrate is first added to the enzyme anti- 

 body fails to inhibit the enzyme action. Conversely, when the antibody 

 is added to the enzyme first, the enzyme fails to catalyze the substrate 

 added last. Lecithin is known to combine with an antigen-antibody 

 complex (Horsf all and Goodner, 1935, 1936).Theinability of lecithin- 

 ase, when in combination with antibody, to hydrolyze lecithin is 

 probably not, therefore, due to an absence of combining affinity of 

 lecithin for the complex. Is this failure of the enzyme due to the failure 

 of the reactive groups of the enzyme and substrate to meet each other? 

 Is antibody incapable of having access to the combining groups of the 

 antigen molecule when the latter is reacting with its specific substrate? 

 Since the enzyme-substrate combination is a continuously reversible 

 one, and since the antigen-antibody combination is also very rapid and 

 produces a relatively stronger union, or only a very slightly reversible 

 one, one is inclined to assume that there should be repeated occasions 



