ABSTRACT
We studied interaction between S-ethynyl ethers of phosphorus acids with cytochrome P-450 from rat liver and housefly abdomen. High thionic effect, i.e., considerable selectivity for the studied compounds in homoiotherms and arthropods, proved to the related to the triple bond in these compounds. Apparently, cytochrome P-450 participates in S-ethynylthiophosphates metabolism and breaks the P-S bond. This gives rise to "self-destroying" metabolites, namely, alkylthioketenes, which decelerate deactivation reactions through destruction of the corresponding isoform of cytochrome P-450 in the microsomal fraction in both homoiotherms and insects. However, the activation reaction goes much faster in insects than in homoiotherms.
Subject(s)
Alkynes/metabolism , Cytochrome P-450 Enzyme System/metabolism , Microsomes/metabolism , Organothiophosphorus Compounds/metabolism , Animals , Houseflies , In Vitro Techniques , Microsomes/enzymology , Microsomes, Liver/enzymology , Microsomes, Liver/metabolism , Rats , Species SpecificityABSTRACT
Here we present data on the anticholinesterase activity of 58 synthesized ethers of phosphorus thioacids with an acetylene bond in the thioether group. Anticholinesterase activity of the compounds, with acetylene group in beta and especially alpha position, in the thioether radical is many times that of their saturated analogs. Reaction between the enzymes and acetylene organophosphorous inhibitors, as well as their saturated analogs, results in phosphorylated enzyme. The triple bond plays a significant role in the acceleration of cholinesterases phosphorylation. Antienzyme activity of acetylene organophosphorous inhibitors is discussed.