Organophosphate inhibitors: The reactions of bis(p-nitrophenyl)methyl phosphate with liver carboxylesterases and α-chymotrypsin

Hamilton S.E., Dudman N.P.B., De Jersey J., Stoops J.K. and Zerner B. (1975) Organophosphate inhibitors: The reactions of bis(p-nitrophenyl)methyl phosphate with liver carboxylesterases and α-chymotrypsin. BBA - Enzymology, 377 2: 282-296. doi:10.1016/0005-2744(75)90310-1


Author Hamilton S.E.
Dudman N.P.B.
De Jersey J.
Stoops J.K.
Zerner B.
Title Organophosphate inhibitors: The reactions of bis(p-nitrophenyl)methyl phosphate with liver carboxylesterases and α-chymotrypsin
Journal name BBA - Enzymology
ISSN 0005-2744
Publication date 1975-02-19
Sub-type Article (original research)
DOI 10.1016/0005-2744(75)90310-1
Volume 377
Issue 2
Start page 282
End page 296
Total pages 15
Subject 2700 Medicine
Abstract Bis(p-nitrophenyl) methyl phosphate (BNMP) has been tested as a spectrophotometric titrant for a group of serine hydrolases. Bis(p-nitrophenyl) methyl phosphate reacts rapidly with liver carboxylesterases from chicken, sheep, and horse, and more slowly with α-chymotrypsin, releasing 2 mol of p-nitrophenol per active site titrated, and producing a phosphorylated enzyme very stable to dephosphorylation. However, pig liver carboxylesterase produces 2.2 mol of p-nitrophenol per active site titrated. Reaction of pig and chicken liver carboxylesterases with bis(p-nitrophenyl) [3H]methyl [32P]phosphate clarified this difference. One molecule of the chicken enzyme reacts with one molecule of bis(p-nitrophenyl) methyl phosphate, releasing both p-nitrophenol residues, and resulting in an inhibited enzyme with one phosphorus atom and one methyl group covalently bound. Pig enzyme reacts rapidly, forming (presumably) methyl p-nitrophenyl phosphoryl-carboxylesterase. This further reacts, concurrently producing methyl phosphoryl-carboxylesterase plus p-nitrophenol, or free enzyme plus methyl p-nitrophenyl phosphate, in the ratio of about 5:1 at pH 7.55. The free enzyme produced undergoes further reaction with bis(p-nitrophenyl) methyl phosphate until all the carboxylesterase is inhibited.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import - Archived
 
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