Inhibition of Xenobiotic-Degrading Hydrolases by Organophosphinates
Abstract
Pretreatment of mice by intramuscular injection of 4-nitrophenyl diphenylphosphinate inhibited 89% of liver carboxylesterase activity in 2h. Hydrolysis of aspirin was not reduced in pretreated mice, although a transient increase in the salicylic acid hydrolysis produce was observed. Pretreatment with 4-nitrophenyl methyl(phenyl)phosphinate had no significant effect on total liver carboxylesterase activity or on the metabolism of aspirin. Rabbit serum arylester hydrolase, which hydrolyzed 10 or 13 organophosphinates tested as substrates, was partially inhibited by 4-nitrophenyl isoprophy(phenyl) phosphinate and 4-nitrophenyl diphenylphosphinate, which were not substrates. Bovine pancreatic trypsin and chymotrypsin were stero-selective in reactions with 4-nitrophenyl isopropyl(phenyl)phosphinate, with more rapid loss of the longer retained enantiomer in high performance liquid chromatography employing the chiral phase D-3, 5-dinitrobenzoylphenylglycine. Trypsin, but not chymotrypsin, exhibited a similar stereo-selective reaction with 4-nitrophenyl ethyl(phenyl)phosphinate; hydrolysis of this phosphinate was catalyzed with the same stero-selectivity by arylester hydrolase.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1985
- Accession Number
- ADA200035
Entities
People
- James K. Zimmerman
- James M. Joly
- John R. Grothusen
- P. K. Bryson
- Thomas M. Brown
Organizations
- Clemson University