title: [Enzymatic detoxication of organophosphorus insecticides and nerve gases in primates].
abstract: The detoxication of organophosphorus compounds by phosphorylphosphatases was studied in primates. Taking into account the distribution of paraoxonase (EC 3.1.1.2) and DFPase (EC 3.8.2.1) in different tissues of the monkey (Macaca mulatta), the total detoxicating capacity for diethyl-p-nitrophenylphosphate (paraoxon, E 600) and diisopropylphosphorofluoridate (DFP) was determined. Acetylcholinesterase (AChE) (EC 3.1.1.7) of human brain was inhibited in vitro by paraoxon and DFP. Using the rate constants of AChE-inhibition and of AChE-synthesis those concentrations of organophosphorus inhibitors were calculated, which in vivo would reduce the steady-state AChE-activity to 20% of normal. This acute ineffective concentration is 7.6 X 10(-8) g/kg for DFP and 2.3 X 10(-8) g/kg for paraoxon. From substrate kinetics of the phosphorylphosphatases the time course of paraoxon and DFP detoxication in primates could be calculated. The time needed by phosphorylphosphatases to reduce a certain dose of an organophosphorus compound to the acute ineffective concentration is referred to as "effective detoxication time". The effective detoxication time (teff) was determined for different concentrations of paraoxon and DFP and was compared with the time needed by these organophosphate concentrations to inhibit AChE-activity to 12.5% of normal (t1/8). The significance of in vitro data for the evaluation of dose limits of organophosphate toxicity in vivo is discussed.
mesh_terms: D000110:Acetylcholinesterase; D000818:Animals; D043303:Aryldialkylphosphatase; D002421:Caudate Nucleus / Q000201:enzymology; D002619:Chemical Warfare Agents / Q000378:metabolism*; D002800:Cholinesterase Inhibitors; D004950:Esterases; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D008658:Inactivation, Metabolic; D007306:Insecticides / Q000378:metabolism*; D007700:Kinetics; D008253:Macaca mulatta; D009943:Organophosphorus Compounds / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D044345:Phosphoric Triester Hydrolases
chemical_list: D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D009943:Organophosphorus Compounds; D006867:Hydrolases; D004950:Esterases; D000110:Acetylcholinesterase; D010744:Phosphoric Monoester Hydrolases; D044345:Phosphoric Triester Hydrolases; D043303:Aryldialkylphosphatase; C020061:diisopropyl-fluorophosphatase
vernacular_title: Die enzymatische Entigiftung von phosphororganischen Insektiziden und Nervengasen in Primaten.