Interaction of the four stereoisomers of soman (pinacolyl methylphosphonofluoridate) with acetylcholinesterase and neuropathy target esterase of hen brain.
Dilute solutions in cold dry ethyl acetate of 98-100% pure specimens of each of the four stereoisomers of soman were tested against enzymes in hen brain homogenate at 37 degrees and pH 8.0. Rate constants for progressive inhibition of acetylcholinesterase were 10(7)-10(8)/mole/min for both P(-) isomers and less than 10(5) for both P(+) isomers. All isomers inhibited neuropathy target esterase non-progressively to some degree. Rate constants for progressive inhibition of neuropathy target esterase were 2.7-3.8 X 10(5)/mole/min for C(-) P(+) and 2-6 X 10(4) for the others. Forced reactivation by KF was 90% initially and aging was slow in each case. Spontaneous reactivation of inhibited neuropathy target esterase was substantial during 18 hr for both P(-) isomers but not for P(+). By comparison of rate constants for the two enzymes we predict that pure P(+) isomers may cause delayed neuropathy in hens dosed at about unprotected LD50: prophylaxis and therapy against acute cholinergic effects would have to raise LD50 1000-fold before birds could tolerate potentially neuropathic doses of P(-) isomers.
D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002645:Chickens; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004789:Enzyme Activation; D005260:Female; D007928:Lethal Dose 50; D009943:Organophosphorus Compounds / Q000633:toxicity*; D012999:Soman / Q000633:toxicity*; D013237:Stereoisomerism
D002800:Cholinesterase Inhibitors; D009943:Organophosphorus Compounds; D012999:Soman; D002265:Carboxylic Ester Hydrolases; C021859:neurotoxic esterase; D000110:Acetylcholinesterase