THE DESTRUCTION OF O,O-DIETHYL-S-2-DIETHYLAMINOETHYL PHOSPHOROTHIOLATE BY LIVER MICROSOMES

Abstract

Liver homogenates prepared from the rat, rabbit, mouse, and guinea pig possess an enzyme system capable of destroying O,O-diethyl-S-2-diethylaminoethyl phosphorothiolate at the rate of 150 to 200 μg/hr/g of fresh tissue. The homogenates prepared from the pig, dog, cow, and frog destroyed this compound at a rate of 50 to 100 μg/hr/g, but those prepared from man and the cat possessed negligible activity. Rat plasma, brain, kidney, diaphragm, whole gut, and spleen also possessed little or no activity. This enzyme system is located in the microsomes, disruption of which is accompanied by loss of enzymatic activity. The activity is dependent upon oxygen, inorganic phosphate, and diphosphopyridine nucleotide. Inhibitor studies indicate that enzymic SH-groups are necessary. The enzyme has no action on diisopropyl phosphorofluoridate, isosystox, or tetraethyl pyrophosphate, although these compounds are rapidly destroyed by the liver.