ANTI-ENZYME IMMUNITY 335 



Attention may be called to a basic principle in enzyme reactions tbat 

 all reversible inhibitors whose action is upon the same enzyme center 

 as normally would combine with substrate molecules are necessarily 

 competitive inhibitors. The degree of competition will naturally vary, 

 but whether it be considerable or very slight, there is no basic differ- 

 ence in the kinetic mode of action. 



J. IMMUNITY AGAINST THE ENZYMATIC ACTIVITIES OF 

 BACTERIAL TOXINS 



1. Bacterial Toxins 



Effects on animal organs in vitro by snake venom poisons were 

 found to be accounted for by the formation of hemolytic lysolecithin 

 which was believed to afford a satisfactory basis for their effect in vivo. 

 Neill and Fleming (1927) reported that sterile filtrates of CI. hotuli- 

 num exercised a lipase activity. Fleming and Neill (1927) found that 

 CI. welchii likewise exercised the power of hydrolyzing tributyrin. 

 They did not, however, mention whether or not these filtrates were 

 also active on lecithin. It is due to the careful work of MacFarlane 

 and Knight (1941) that we have a clear picture of the relation of the 

 lecithinase activity of the toxins of CI. welchii to their hemolytic and 

 other toxic properties. Since this work toxins have been obtained in 

 crystalline form and their properties determined. These and other re- 

 lated studies will be discussed below. 



a. Type A Toxin of Clostridium hotulinum. Lamanna, et al. 

 (1946a, 1946b) described a method for the isolation of a highly toxic 

 needle-shaped crystalline protein from a type A culture of Clostridium 

 hotulinum. Electrophoretic analysis showed homogeneity and a mo- 

 bihty of 2.75XlO~^cm^.volt~^sec.~^ The sedimentation diagram 

 showed a single symmetrical boundary in the ultracentrifuge, yielding 

 a value of S20=17.3 Svedberg units. The diffusion constant by the re- 

 fractometric scale method was 2.14XlO~'^cm.Volt~^sec.~^. From these 

 data a molecular weight of 900,000 was calculated (Putnam, Lamanna 

 & Sharp, 1946). It contained 14.3 per cent nitrogen. The Molisch test 

 was negative. The pure toxin is a protein with the solubility properties 

 of globulin. One MLD (mouse) contained 4.2XlO~Vg nitrogen, or 

 3X10~^ mg. of toxin. The data suggest that there are 2.1X10"^ mole- 



