ACETIC ACID AND ACETATE 259 



isomer. In harmony with this observation, isovalerate was found to give 

 rise to more acetyl groups than was the case with n-valerate.^* Undecylic 

 acid, labeled with deuterium on carbons 10 and 11, did not yield acetyl.^' 



In general, the odd-carl)on acids are believed to be degraded by )3- 

 oxidation to a C3 (propionic acid) fragment, which can be converted to 

 carbohydrate,** and to a two-carbon unit which can comV)uie to form 

 acetoacetate.^'' However, the resulting ketonuria will be determined by 

 the relative proportion of ketogenic and ketolytic molecules. The longer 

 the odd-chain acid, the greater will be the proportion of acetoacetate 

 formed in comparison with the carbohydrate originating from propionate. 

 This is in harmony with the observation that practically no ketonuria 

 results in fasting rats fed valeric acid, and only small amounts obtain 

 after sodium heptanoate is fed.-^'-'* 



c. Formation from Pyruvate. Although a number of investigators have 

 demonstrated the conversion of pyruvic acid to acetic acid both aerobi- 

 cally"'^^ and anaerobically by dismutation,^^'"*" this does not appear to be 

 the main pathway of breakdown, as the acetic acid is oxidized very slowly. 

 The oxidation product of pyruvate is in all probability a two-carbon com- 

 pound more active than acetate. A phosphoroclastic splitting of pyruvate 

 into acetylphosphate and formate, or CO2 + H2O, which Lipmann^^ 

 observed in Bacillus acidificans longissimus {Lactobacillus delbruecki) 

 from fermenting mash, would meet the qualifications. This type of split- 

 ting has not been demonstrated in animal tissue. 



There are several examples of the accumulation of acetate following the 

 metabolism of pyruvate. Thus, Barron et al^^ reported the formation 

 of acetate when kidney or liver slices oxidized pyruvate in the presence of 

 fluoroacetate. It was suggested that acetate fails to be oxidized because 

 of competition of fluoroacetate with the active enzyme.^* Bloch^ suggests 

 that fluoroacetate may exert its inhibiting effect by blocking condensations 

 involving the reactive acetyl compound, which then becomes stabilized as 



" K. Bloch, /. Bwl. Chem., 155, 255-263 (1944). 



^* G. Lusk, The Elements of the Science of Nutrition, 4th ed., Saunders, Philadelphia 

 and London, 1928, pp. 219, 660. 



36 E. M. MacKay, A. N. Wick, and C. P. Barnum, /. Biol. Chem., 136, 503-507 (1940). 

 " H. A. Krebs and W. A. Johnson, Biochem. J., 31, 645-660 (1937). 



38 C. Long, Biochem. J., 32, 1711-1717 (1938). 



39 H. Weil-Malherbe, Biochem. J., 31, 2202-2216 (1937). 

 « F. Lipmann, Skand. Arch. Physiol., 76, 255-272 (1937). 



*i F. Lipmann, Cold Spring Harbor Symposia Quant. Biol., 7, 248-259 (1939). 

 « E. S. G. Barron, G. R. Bartlett, and G. Kalnitsky, Federation Proc, 5, 120-121 

 (1946). 



" G. R. Bartlett and E. S. G. Barron, ./. Biol. Chem., 170, 67-82 (19471 



