Inhibition of Xenobiotic-Degrading Hydrolases by Organophosphinates.
Abstract
Organophosphinate pretreatment agents for chemical warfare defense inhibited carboxylester hydrolase from porcine liver and from rabbit liver. Recovery of rabbit liver monomeric carboxylester hydrolase to at least 30% of its initial activity was observed 48 hr. after inhibition by certain 4-nitrophenyl alkyl(phenyl)phosphinates and analogues. When ranked according to the initial rates at which their phosphinylated enzymes recovered, they were methyl(phenyl)>methyl(2-thienyl)>methyl(2-furyl)>ethyl(phenyl)>di-2-thienyl>diphenyl. Recovery was less than 20% in 96 hr. following inhibition by methyl(naphthyl),di-2-furyl, isopropyl(phenyl), dichloromethyl(phenyl), and bis chloromethyl substituted analogues. High performance liquid chromatography on silica using 10% to 20% 2-propanol in hexane as mobile phase resulted in satisfactory chromatograms for all except the most polar phosphinates. This method was useful in determining purity and decomposition of the compounds. Arylester hydrolase was purified 30-fold from rabbit serum by a sequence of polyethylene glycol fractionation, ion exchange chromatography, ammonium sulfate fractionation, molecular exclusion chromatography and pseudo-affinity chromatography. The partially purified enzyme was activated by 2.5 mM divalent calcium.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1983
- Accession Number
- ADA139650
Entities
People
- J. K. Zimmerman
- J. R. Grothusen
- P. K. Bryson
- T. M. Brown
Organizations
- Clemson University