CELLULAR METABOLISM I23 



et al. (81) maintain that a-ketoglutarate is oxidized to succinate by 

 preparations from pigeon breast muscle without the necessity of in- 

 organic phosphate, adenosinetriphosphate, and magnesium, all com- 

 ponents considered by Ochoa essential for the oxidation process. The 

 phosphorylations in the first step of the cycle (see chart) — pyruvate -f- 

 y202—> acetate + CO2 — have not been established in animal tissues in 

 spite of the repeated efforts of Lipmann (54). Here again, Stumpf et al. 

 maintain that this oxidation occurs in the absence of phosphate and 

 with no formation of acetyl phosphate. The second oxidation step, iso- 

 citrate + TPN ^ oxalosuccinate + TPN H2, is postulated to give no 

 high-energy phosphate bonds; however in the experiments of Ochoa 

 (69) there was but one step in the transfer of electrons. If Ball's sug- 

 gestion is verified, here as well as in the oxidation of pyruvate, the step 

 by step release of energy might be utilized for the formation of high- 

 energy phosphate bonds. In the fourth step, succinate + ^Og ^ fuma- 

 rate + H2O, there has been found evidence of one phosphorylation 

 (66). This is probably due to the high potential of the system (o V. at 

 pH 7) and the fewer steps in electron transport to molecular oxygen 

 (0.8 v.). The final step, malic + ^02 ^oxaloacetic + H2O, was found 

 by Kalckar (40, 41) to produce at least two phosphorylations. It seems 

 as if the insistence on finding analogs to Warburg's reaction, which after 

 all is a fermentation reaction, has stopped progress and hindered the 

 search for other channels of energy transfer. Perhaps Ball's suggestion 

 ought to be studied experimentally. Aerobic phosphorylations may be 

 produced by the release of energy from the different oxidation-reduction 

 catalysts to adenylic acid, for it is accepted that adenylic acid enhances 

 completeness of oxidation. Lack of phosphorylation in isolated enzyme 

 systems where substrate is oxidized by only the first oxidation-reduc- 

 tion system and failure of phosphorylation in some tissue extracts when 

 cytochrome C is not present favor this opinion. The ATP thus produced 

 would represent the free useful energy ready to be used. 



Energy transfer from electrons and its utilization by the cell through 

 adenosinetriphosphate occurs not only on the oxidation of carbohydrates 

 but also on that of fats, as the studies of Lehninger (50) and Munoz 

 and Leloir (64) have demonstrated. 



The Oxidation and the Synthesis of Fats 



Our knowledge of the mechanism of oxidation and synthesis of fatty 

 acids has advanced considerably in the last years through the efforts of 



