Carboxylesterases, importance for detoxification of organophosphorus anticholinesterases and trichothecenes.
Several different types of experiments, including the use of inhibitors, have shown that carboxylesterases are a major factor in the metabolism and therefore detoxification of organophosphorus compounds such as soman and trichothecene toxins. The development of a new assay method for the enzyme has allowed us to separate the carboxylesterases into two major groups. The carboxylesterases can, however, be further separated by gel filtration, affinity chromatography, isoelectric focusing, and chromatofocusing into several isoenzymes. Liver microsomal carboxylesterases can be separated into five or six isoenzymes whereas guinea-pig plasma contains two isoenzymes. The isoenzymes differ in molecular weights, isoelectric points, substrate specificities, and affinity for inhibitors. Intravenous administration of a carboxylesterase preparation lowered the toxicity of soman in young rats. Carboxylesterases from rat and guinea-pig plasma inhibited by soman could be reactivated by DAM, whereas enzymes from porcine liver were not reactivated. Only one of the isoenzymes from rat liver microsomal preparation was responsible for the metabolism of T-2 toxin to HT-2. The further metabolism of HT-2 was performed by esterases from rat liver cytoplasma. Long-term exposure of the bronchial muscle to low concentration of soman modulate the bronchial contraction.
D000818:Animals; D001980:Bronchi / Q000187:drug effects; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000378:metabolism* / Q000633:toxicity; D002850:Chromatography, Gel; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008658:Inactivation, Metabolic; D007525:Isoelectric Focusing; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012717:Sesquiterpenes / Q000378:metabolism*; D012999:Soman / Q000633:toxicity; D013045:Species Specificity; D014255:Trichothecenes / Q000378:metabolism* / Q000633:toxicity; D014317:Tritolyl Phosphates / Q000633:toxicity
D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D012717:Sesquiterpenes; D014255:Trichothecenes; D014317:Tritolyl Phosphates; D012999:Soman; D002265:Carboxylic Ester Hydrolases; C025541:tri-o-cresyl phosphate