194 CORI AND CORI an exchange of phosphate between A TP and phosphopyruvate seemed possible. Previous negative results were due to the fact that potas sium ions were not added, K+ being necessary for the transfer of phosphate in the above reaction. Lardy & Ziegler (1) have now demonstrated, by measuring the distribution of p32 and by chemical measurements, that pyruvate and A TP can-form phosphopyruvate in the presence of K+, making unnecessary the assumption that the formation of a 4-carbon compound is an obligatory intermediate. The study of individual reactions of the tricarboxylic acid cycle (which is concerned with the oxidation of carbohydrate and fat) has been continued by Ochoa (2, 3). Using heart muscle extract, he has found that the oxidation of isocitric to a-ketoglutaric acid involves two enzymatic reactions, both of which are reversible. The first reaction, catalyzed by isocitric dehydrogenase, yields oxalosuccinate in the presence of TPN. The second reaction, oxalosuccinate a-ketoglutarate+ CO2, requires Mn++ and its discovery represents an important advance in our knowledge of the biological utilization of carbon dioxide. The isocitric dehydrogenase system is linked to the cytochrome system through cytochrome-c reductase which cata lyzes the reoxidation of reduced TPN by cytochrome-c (4). In previous work on carbon dioxide fixation in animal tissues· the assumption was made that pyruvate reacts with carbon dioxide to form oxaloacetate. The fixation of (1302 by pigeon liver extract, with pyruvate and fumarate as substrates, has been investigated by Wood et al.(5). The isotopic carbon was found in the carboxyl groups of fumarate, malate, pyruvate, and lactate in about equal con centrations, but an attempt to demonstrate an exchange between ClS02 and oxaloacetate gave a negative result. This left open the question of the primary product of the fixation reaction, although. the results did not exclude the reaction previously proposed, namely, pyruvate+ CO2 oxaloacetate. Direct proof for this reaction in animal tissues (it had been demonstrated before in bacteria) has now been obtained by Utter & Wood (6). They found C'8 in the car boxyl group of oxaloacetate adjacent to the methylene group when pigeon liver extract was incubated anaerobically with pyruvate, oxalo acetate, Mn++, NaHCI3Oa, and ATP. Addition of ATP increased the fixation of carbon dioxide in dialyzed extracts, but it is not yet clear how it participates in the reaction. Two coenzyme-linked reactions which lead to the formation of oxaloacetate or oxalosuccinate (the intermediates which are in equi-