Phenazine compounds as carriers in the hexosemonophosphate system

CERTAIN phenazine compounds resemble the flavins in that they can readily form semiquinones, to which property, generally very rare in dyestuffs, Michaelis et al. [1936, 1, 2] attach much importance in determining the catalytic activities of the flavin enzyme and vitamin B2.Phenazine methiodide [Dickens, 1936, 1] like pyocyanine [Friedheim, 1934] and certain flavin compounds [Laser, 1934] has an action on tissue metabolism which is quite different from that of most of the usual oxidation-reduction dyestuffs [Dickens, 1936, 1].In tissues exhibiting strong aerobic glycolysis, particularly tumour tissue, the respiration is increased and the aerobic glycolysis falls in the presence of these compounds which thus appear to exert a control of the Pasteur reaction [cf.Dickens, 1936, 2].While the action of the simpler phenazines is rapid, enabling its detection in short experiments by the tissue- slice method, that of the flavins can only be demonstrated in tissue culture experiments, presumably owing to slow absorption or slow transformation into the active carrier.On the other hand the easily diffusible phenazines cause some inhibition of the anaerobic glycolysis also [Dickens, 1936, 1], so that this is not a simple augmentation of the Pasteur effect.This group of substances produces such unusual effects that an attempt has been made to elucidate the mechanism of their action by a study of the catalytic role of the phenazines in an isolated enzyme system.Weil-Malherbe [1937, 2] has studied the action of phenazine methochloride and pyocyanine in the oc-hydroxyglutaric system.In the experiments described below we have prepared some new phenazine compounds and used them as substitutes for the flavin enzyme of Warburg in the hexosemonophosphate system, comparing their catalytic activities with those of other carriers.We have also measured the oxidation-reduction potentials of a number of phenazines for correlating our results.The experiments reveal new aspects of the common features of the phenazines and flavin compounds, and it is shown that in the hexosemonophosphate system the catalytic activity of some of these compounds much surpasses that of the ordinary oxidationreduction dyestuffs studied.Green et al. [1934] used pyocyanine as carrier in this system in their studies on carrier-linked reactions.Later Ogston & Green [1935] stated their objections to the description of the flavin- phosphate-protein complex as an enzyme.In the following we have retained the term flavin enzyme, since the question cannot be regarded as settled., Enzyme and s8ubtrate preparations Enzyme preparations.Many of the experiments were made on preparations of "'Zwischenferment" [Negelein & Gerischer, 1936] and coenzyme II of purity 1, generously supplied by Prof. Warburg, who also gave us a sample of flavin ( 1615 )