XCVII. PYRUVATE OXIDATION IN BRAIN V. EVIDENCE DERIVED FROM THE METABOLISM OF a-KETOBUTYRIC ACID

THE problem of the specificity of the pyruvate oxidation system in pigeon's brain tissue has been studied more fully by us, not only in the hope that it would throw fresh light upon the path of complete oxidation of pyruvic acid, but also in the belief that knowledge of the behaviour of other simple oc-ketoacids would contribute further to the elucidation of the metabolism of some of the oxidation products of the ac-amino-acids. In particular it was hoped that some definite indication would be obtained as to whether the three reactions found to account quantitatively for the aerobic oxidation of pyruvic acid [Long, 1938] were entirely separate or were interrelated. This objective, we think, has been realized. We have now obtained evidence that the rate of oxidation (p mol./hr.) is the same for pyruvic acid and ac-ketobutyric acid; but whereas the latter gives as end-product C02 and presumably the next lower fatty acid, a change requiring 1°O per mol., part of the pyruvic acid disappearing is much more fully oxidized. This suggests that there is a common path for the initial stage in the oxidation, intermediate compounds of similar type being formed from pyruvic and oc-ketobutyric acids, the sole difference being that in the case of pyruvic acid a further system intervenes capable of oxidizing this unstable intermediate to C02 and water. The intermediate formed from oc-ketobutyric acid can only break down without 0° uptake to C02 and, by analogy, propionic acid. Hence the scheme for pyruvic acid oxidation suggested by Long [1938]