ENZYMES CONCERNED WITH DIGESTION OF LIPIDS 41 



most active; it was found to have 30 times the activity of eserine. The 

 most potent alkyl fluorophosphonate inhibitors were the esters with short 

 branched-chain alkyl groups. The order of inhibitory power of the various 

 esters was roughly the same as that for toxicity and myotic power. Webb 238 

 reported that brain cholinesterase (type e) was inhibited by an alkyl fluoro- 

 phosphonate, but not to the same extent as was serum cholinesterase. 

 Liver esterases, human milk lipase, and kidney phosphatase were likewise 

 sensitive to fluorophosphonate, but the amount required was much greater 

 than in the case of cholinesterase. No correlation was shown to exist be- 

 tween the sensitivity of the non-choline esterases toward fluorophosphonate, 

 toward eserine, and toward sodium fluoride. For example, liver esterase is 

 highly sensitive to fluorophosphonate but relatively insensitive to eserine. 



Different amounts of DFP are required to effect the inhibition of cholin- 

 esterase in both in vivo and in vitro tests. For example, Nachmansohn 

 et al. 239 state that, while inhibition of cholinesterase in vitro requires only 

 micrograms of DFP, the inhibition of cholinesterase in axonal conduction 

 requires milligrams. These workers explain this discrepancy by the fact 

 that a lipid membrane surrounds the axon and acts as a barrier to the en- 

 trance of DFP ; a considerable difference exists in the concentration of the 

 inhibitor inside and outside the membrane at the time of action. Similar 

 variations in sensitivity of DFP in vitro and in vivo were noted earlier by 

 Mazur and Bodansky. 240 



Inhibition with DFP is reversible for a certain period, depending upon 

 temperature and upon the concentration of the inhibitor. A close parallel- 

 ism was observed in the interval required in different nerve preparations, at 

 several temperatures, between the irreversible destruction of cholinesterase 

 and the irreversible abolition of conduction. Freedman and co-workers 241 

 reported that the rate of regeneration of non-specific plasma cholinesterase 

 after large doses of DFP is more rapid than is that of the specific cholin- 

 csterases in the erythrocytes and brain. A lag in the regeneration of the 

 cholinesterase activity in the erythrocyte occurs for twenty-four to forty- 

 eight hours after the injection of DFP, during which time brain cholin- 

 esterase regenerates rapidly. Subsequently, the rate of regeneration of red 

 blood cell cholinesterase becomes more rapid, and exceeds that of the brain. 

 These workers 241 observed that a close relationship appears to exist be- 

 tween the degree of toxicity of DFP and the level of brain cholinesterase 



238 E. C. Webb, Biochem, J., 4®, 96-98 (1948). 



239 D. Nachmansohn, M. A. Rothenberg, and E. A. Feld, Arch. Biochem., 14, 197-211 

 (1947). 



2,0 A. Mazur and O. Bodansky. ./. Biol. Chem., 163, 261-276 (1946). 



211 A. M. Freedman, A. Willis, and II. E. Himwich, Am. J. Physiol, 157. 80-87 (1949). 



