Elsevier

Biochemical Pharmacology

Volume 41, Issues 6–7, 15 March–1 April 1991, Pages 955-959
Biochemical Pharmacology

Phosphonylation of purified human, canine and porcine cholinesterase by soman: Stereoselective aspects

https://doi.org/10.1016/0006-2952(91)90201-FGet rights and content

Abstract

Cholinesterases (EC 3.1.1.8, acylcholine acylhydrolase) from the sera of man, dog and pig were purified 400–600-fold using a combination of ion-exchange and affinity chromatography. In a first approach, phosphonylation by soman was studied by using the half-resolved epimers C(+)P(±)-soman and C(−)P(±)-soman. The degradation of soman at the nanomolar level was followed in time by determining the remaining soman by capillary gas chromatography with NP detection. In the three sera investigated the P-(−)-epimer phosphonylates at a higher rate than its corresponding P(+)-counterpart and the stereoselectivity is greater for the C(+)-epimers than for the C(−)-epimers. Individual soman isomers were isolated from C(+)- and C(−)-epimers and quantified by gas chromatography. Second-order rate constants were determined for the phosphonylation of purified cholinesterase by isolated soman isomers. The C(+)P(−)-isomer has the highest phosphonylation rate for the three species; the other toxic isomer, C(−)P(−), has a five to ten-fold lower rate. The overall stereoselectivity is more marked in human cholinesterase than in canine. Porcine serum cholinesterase is phosphonylated by the P(−)-isomers at a slightly higher rate than the human enzyme.

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Present address: F. A. Janssens Memorial Laboratory of Genetics, Catholic University of Leuven, B-3000 Leuven, Belgium.

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