38 II. DIGESTION AND ABSORPTION OF FATS 



stein 223 suggests that these differences in kinetic behavior indicate that alka- 

 loids in general combine with only one locus of an enzyme active center 

 containing two loci, but that the urethane-like substrates interact with 

 both loci. 



In the case of DFP, Nachmansohn and his co-workers 224 have reported 

 that the enzyme inhibition results from a stoichiometric reaction with the 

 inhibitor. Michel and Krop, 225 using DFP with radiophosphorus, demon- 

 strated that the inhibition of cholinesterase is associated with the binding 

 of DFP phosphorus by the enzyme. According to Jansen et aZ., 226 when a 

 preparation of purified plasma cholinesterase was inhibited by radioactive 

 DFP, the phosphorus of the inhibitor was introduced into the inhibited 

 enzyme. The amount of P introduced into the still impure cholinesterase 

 was 0.0023%. 



Aldridge 227 has postulated that, since organophosphorus inhibitors are 

 esters, they can attach themselves to the active centers of cholinesterase in 

 the same way as do carboxylic esters. The inhibitor is then hydrolyzed, 

 but the enzyme remains phosphorylated, instead of both products passing 

 into solution. The enzyme phosphate so formed has its own stability to 

 hydrolysis, and this is dependent upon the groups attached to the P atom. 

 According to this hypothesis, the potency of the inhibitors is a reflection 

 not of an especially high affinity for the enzyme, but rather of the fact that 

 one active center is inactivated after reaction with one inhibitor molecule. 



The dimethylcarbonate of (2-hydroxy-5-phenylbenzyl)trimethylammo- 

 nium bromide has been shown by Myers 228 to be a reversible inhibitor 

 which combines with the enzyme active center of pseudocholinesterase on an 

 equimolecular basis. 



The explanation of Wilson 229 for inhibition caused by tetraethyl pyro- 

 phosphate : 



C 2 H 5 OC 2 H 5 



\ / 



P-O-P 



/\ Y\ 



C0H5O O O OC0H5 



abbreviated as TEPP, differs somewhat from the other hypotheses of the 

 action of inhibitors. Acetylated cholinesterase, which is an intermediate 



224 D. Nachmansohn, M. A. Rothenberg, and E. A. Feld, ./. Biol. Chem., 174, 247-256 

 (1948). 



22 *H. O. Michel and S. Krop, J. Biol. Chem., 190, 119-125 (1951). 



226 E. F. Jansen, R. Jang, and A. K. Balls, J. Biol. Chem., 196, 247-253 (1952). 



227 W. N. Aldridge, Biochem. ./.. 54, 442-448 (1953). 



228 D. K. Myers, Biochem. J., 51, 303-311 (1952). 



239 J. B. Wilson, ./. Biol. Chem., 190, 111-117 (1951). 



