42 II. DIGESTION AND ABSORPTION OF FATS 



during the regeneration period. The relationship between the toxic signs 

 and the level of e-cholinesterase is less exact than in the case of the brain 

 cholinesterase ; no relationship was noted between the level of serum cholin- 

 esterase (s) and the extent of toxicity. Freedman and Himwich 242 like- 

 wise observed a correlation between the clinical signs of DFP poisoning in 

 rats and the level of brain cholinesterase. The more severe symptoms were 

 noted when the cholinesterase level in the brain was greatly depressed. 



Anti-inhibitors are known which can protect cholinesterase from DFP. 

 Cohen, Warringa, and Bovens 243 reported that butyrylcholine prevented 

 the irreversible inactivation of cholinesterase by DFP. It was shown that 

 butyrylcholine is probably a competitive inhibitor of true cholinesterase; 

 it acts reversibly. However, it was impossible to alter the lethal effects 

 of DFP in rats by administering butyrylcholine before or after DFP. 

 Wright and Mendel 244 reported the presence of a substance in incubated 

 heart preparations which had the ability to increase the activity of cholin- 

 esterase on fresh heart pulp. It is suggested that this effect could result 

 from the formation of an activator, or from the production of a substance 

 which neutralizes the action of a naturally-occurring cholinesterase in- 

 hibitor. Resistance to the action of DFP in rats is increased with age, 242 

 up to 120 days. 



(d') Miscellaneous Inhibitors. — Bis(isopropylamine)-fluorophosphine ox- 

 ide has been shown by Callaway et al. 2V ° to be a potent cholinesterase in- 

 hibitor both in vitro and in vivo. While recovery of enzyme activity was 

 complete in 40 days after poisoning with DFP, only a 60% recovery was 

 obtained after a similar time interval in animals injected with bis(isopropyl- 

 amino)-fluorophosphine oxide. It is believed that these two inhibitors 

 exhibit different modes of action. 



s 



t 



a C 2 H 5 0— P— O C N 



I I /\/\ 



2 N-<3>-0-P-0C 2 H 5 ( ^° ™ C CH 



C 2 H 5 



HC C CH 



c c 



H H 



(I) (ID 



242 A. M. Freedman and H. E. Himwich, Am. J. Physiol, 153, 121-126 (1948). 



243 J. A. Cohen, M. G. P. J. Warringa, and B. R. Bovens, Biochim. et Biophys. Acta, 6, 

 469-476(1951). 



244 M. Wright and B. Mendel, J. Biol. Chem., 165, 389-390 (1946). 



245 S. Callaway, D. R. Davies, and J. E. Risley, Biochem. J., 50, xxx (1952). 



