The quinine-oxidizing enzyme and liver aldehyde oxidase.

A derivative of quinine formed in minced rabbit liver has been isolated by Kelsey et al. (I), and identified by Mead and Koepfli (2) as a carbostyril. Hence quinine is oxidized in liver with replacement of the hydrogen atom in position 2 of the quinoline ring by a hydroxy group. Analogous oxidation products are excreted by men receiving the four principal cinchona alkaloids. This change is important in the chemotherapy of malaria, because the oxidation of these compounds markedly reduces their antimalarial activity (3). The activity of some quinoline compounds can be greatly enhanced if this oxidation is prevented by appropriate substitution (4). The nature of the metabolic system able to perform this oxidation is consequently of considerable pharmacological interest, and it was hoped that its biochemical function as well could be approached by studying the reaction with a series of quinoline derivatives. By the use of such compounds as substrates, the enzyme responsible for their oxidation has been prepared in about 5 per cent purity. It specifically acts on unsaturated heterocyclic compounds with an active a-hydrogen and is intimately associated with the flavoprotein, liver aldehyde oxidase.