“Coupling” of Phosphorylation With Oxidation of Pyruvic Acid in Brain

An analysis of the dialyzable components of the pyruvic acid oxidation system of brain showed that in addition to cocarboxylase (thiamine pyrophosphate) (2), a C, dicarboxylic acid (2), and magnesium or manganese ions (3), both inorganic phosphate and "adenine nucleotide" (adenylic acid, adenosine triphosphate) (4) are required.The latter observation suggested that a cycle of phosphorylation is involved in the enzymatic oxidation of pyruvate by animal tissues.With acetone-dried preparations of Bacillus delbriickii Lipmann had found that dehydrogenation of pyruvic acid required both cocarboxylase and inorganic phosphate and that, upon addition of adenylic acid, inorganic phosphate disappeared with an equivalent formation of adenosine polyphosphate (5).The two lines of research show that phosphorylation processes take a part in the enzymatic oxidation of pyruvic acid generally.The present research was undertaken to study the relationship between phosphorylation and oxidation of pyruvate in brain.Though esterification of inorganic phosphate with either adenylit acid or creatine accompanies oxidation of pyruvate in brain preparations, its direct demonstration is difficult owing to the presence of adenosine triphosphatase (4).Esterification may be demonstrated, however, if in the presence of catalytic amounts of adenylic acid either hexose monophosphate or glucose is used as phosphate acceptor (1).Aerobic phosphorylation of glucose, and of other P acceptors, has been investigated by Kalckar in kidney preparations (6, 7), and more recently by Colowick, Welch, * Preliminary report (1).