A cholinesterase inhibitor derived from OO-diethyl O-p-nitrophenyl thiophosphate in vivo.

in the urine, and the kidney must have a considerable power of concentrating formate. The inhibition of the appearance of formate during the administration ofethanol is in accordance with Zatman's (1946) interpretation of the earlier experiments, namely, that a primary oxidation of methanol to formaldehyde through the agency of alcohol dehydrogenase is competitively inhibited by ethanol. More recently, Jacobsen (1952) has expressed a doubt as to whether alcohol dehydrogenase is involved in methanol oxidation in tvivo, a doubt based chiefly on the claim of Theorell & Bonnichsen (1951) that pure crystalline alcohol dehydrogenase of horse liver does not react with methanol to any measurable extent. But it has been our experience that cruder preparations of the horse-liver enzyme can easily be shown to reduce diphosphopyridine nucleotide in the presence of methanol; also, for the study of the back-reaction with reduced coenzyme, formaldehyde is in some ways a more convenient substrate to use than is acetaldehyde even with the pure enzyme (Theorell & Chance, 1951). The properties ofthe pure crystalline enzyme are not necessarily more closely relevant to events in vivo than are the properties of the cruder preparation. Jacobsen's altemative suggestion, that the principal mode of oxidation of methanol in vivo may be the catalase-hydrogen peroxide mechanism discovered by Keilin & Hartree (1945), does not at the moment seem to provide a sufficient explanation of the striking inhibitory effect of ethanol. More evidence is required to make it possible to decide whether either of the views so far put forward is correct.