ENZYMES CONCERNED WITH DIGESTION OF LIPIDS 43 



p-Nitrophenyl diethylthiophosphate (I) is an inhibitor which acts on 

 cholinesterase, with a characteristic bimolecular reaction. 246 It is also 

 referred to in the literature as parathion (E 605). On the other hand, 8- 

 quinolyl diethylthiophosphate (II) brings about inhibition by a unimolec- 

 ular reaction. 216 Aldridge and Davison 217 reported that the inhibition of 

 sheep red-cell cholinesterase (c-type) by 6 substituted diethylphenyl 

 phosphate inhibitors produced either a first order or a bimolecular reaction. 

 In the case of dimethyl-p-nitrophenyl phosphate, Aldridge 227 demonstrated 

 that the inhibition of erythrocyte cholinesterase reverses at a measurable 

 rate. According to Diggle and Gage, 248 parathion itself has a low inhibitory 

 action; however, the <S-ethyl isomer (III), with which parathion is usually 



O 



Q 2 N^ ^>— O— P— SCoH 5 



O— C 2 H 5 



(III) 



contaminated, is a highly inhibitory substance. The power of parathion 

 to inhibit cholinesterase is proportional to its content of the *S'-ethyl isomer. 



Paludrine, C1C 6 H 4 NHC( :NH)NHC(:NH)NHCH(CH 3 ) 2 , has been 

 shown to be only weakly effective as a cholinesterase inhibitor. Blaschko 

 el a/. 249 showed that this drug has little affinity for the cholinesterase in the 

 central nervous system; this accounts for its low toxicity. However, some 

 of the other cholinesterases are believed to be more strongly inhibited by 

 paludrine. However, there was no interference in the hydrolyses of 

 methyl butyrate or tributyrin when extracts of rabbit pancreas were treated 

 with a 10 -3 M concentration of paludrine. 



Bain 250 has reported on the inhibitory action of a series of 0-chlorinated 

 amines on the cholinesterase system of rat brain. The enzyme was shown 

 to combine with two moles of acetylcholine to form an inactive complex 

 with a dissociation constant of 1.6 X 10~ 2 M. The structure necessary 

 for the inhibitory action of /3-chlorinated amines was shown to be correlated 

 with that required for convulsant activity. Although the inhibitory action 

 of strychnine and nicotine was confirmed, metrazol and picrotoxin were not 

 found to be inhibitors. Moreover, the anticonvulsant drugs, pheno- 

 barbital, trimethadione, phenacetylurea, diphenylhydantoin, and atropine, 



246 W. N. Aldridge, Biochem. J., 46, 451-459 (1950). 



247 W. N. Aldridge and A. N. Davison, Biochem. J., 51, 62-70 (1952). 



248 W. M. Diggle and J. C. Gage, Biochem. J., 48, xxv (1951); 49, 491-494 (1951). 



249 H. Blaschko, T. C. Chow, and I. Wajda, Biochem. J., 40, lxvii (1946\ 

 260 J. A. Bain, Am. J. Physiol, 160, 187-194 (1950). 



