122 E. S. GUZMAN BARRON 



O 



// 



-C^ OH O 



\ / // 



\^^ +ADP 7-^ -r +ATP 



OH \o_ 



O- 



/ 



-c 



\ 



The resonating structures impart stability to the group (39). 



Lipmann (53) has appHed and extended these concepts to the oxida- 

 tion of pyruvate and a-keto acids in general, and indeed has found that 

 certain bacteria produce acetylphosphate on oxidation of pyruvic acid, 

 and that animal tissues hydrolyze acetylphosphate rather rapidly (54). 

 These important contributions of Lipmann were promptly accepted, 

 but little has been accomplished towards further clarification of the 

 mechanism of aerobic phosphorylations. The fact that they exist was 

 demonstrated by Belitzer and Tsibakowa (15), Ochoa (65) and Colo- 

 wick et al. (24). From Ochoa's work it is clear that on the oxidation 

 of pyruvate there are about 15 phosphorylations per mole of pyruvate 

 completely oxidized, i.e. 3 per atom of oxygen. Of these 15 phosphoryla- 

 tions, Ochoa (66) has reported that during the oxidation of a-keto- 

 glutaric acid to succinic acid in the presence of glucose and adenylic acid, 

 3 phosphate molecules are simultaneously esterified to the sugar forming 

 hexose diphosphate. The transfer of 2 electrons to oxygen was thus 

 accompanied by the release of energy in three successive steps in the 

 form of high-energy phosphate bonds. How they are formed remains 

 unknown. The postulated succinylphosphate formed as the first product 

 of oxidation has not been demonstrated. Ball's suggestion (2) that the 

 step by step transfer of electrons from oxidizable substrate to pyridine 

 nucleotide, from this to flavin, from fllavoprotein to cytochrome, and 

 from cytochrome to oxygen might release the energy (0.25 V.) neces- 

 sary to form a high-energy phosphate bond seems reasonable, but again 

 is still in the realm of speculation. To complicate the problem, Stumpf 



