Pyruvate oxidation in brain

Abstract

Brief dialysis of pigeon brain dispersions greatly reduces their power to oxidize pyruvate; full reactivation can be obtained by addition of inorganic phosphate + a C4 dicarboxylic acid (succinate, fumarate, malate) + adenine nucleotide. The same is true for dispersions of rabbit brain. In the presence of the other components of the system, adenine nucleotide not only increases the oxidative removal of pyruvate but makes its oxidation more complete. Whereas in the absence of adenine nucleotide the ratio mol. O2 taken up/mol. pyruvate removed is 0.75, in its presence, the ratio is increased to 1.5 (at 28[degree]). The ratio mol. O2/mol. pyruvate of the excess metabolism produced by adenylic acid is 2.1, i.e., near the theoretical value of 2.5 for complete oxidation of pyruvate to CO2 + H2O. Cozymase can replace adenylic acid and (in pigeon''s brain dispersions) the former is, molecule for molecule, even more active than the latter; this is probably due to enzymic splitting of cophosphorylase ("adenine nucleotide"). In rabbit''s brain dispersions, cozy- mase replaces adenylic acid only after periods of dialysis not exceeding 1.5 hr. After 4.5 hr. dialysis this is no longer the case. The possibility that cozymase, acting as code-hydrogenase, may be required at some stage of pyruvate oxidation is discussed. Phosphoglycerate is oxidized by pigeon brain dispersions almost as readily as is pyruvate, due to its rapid conversion into pyruvate + H3PO4. The formation of phosphopyruvic from phosphoglyceric acid, in brain dispersions, and the transfer of phosphate from phosphoglyceric to adenylic acid, in brain extracts occur in the same way as in skeletal muscle. Citrate or [alpha]-keto-glutarate are much less active than any of the Cd4 dicarboxylic acids in catalysing the oxidation of pyruvate by brain dispersions. The necessity of fumarate and adenylic acid for the oxidation of pyruvate by kidney cortex dispersions (rabbit) was demonstrated.