272 VI. ACETIC, FORMIC, AND PROPIONIC ACIDS 



(a) Succinic Acid. Thunberg^-^ wasthe first to suggest that succinic acid 

 might arise by the hnking of the methyl groups of two acetate molecules 

 as given below: 



HOOC-CH2iH"+ HiCH2C00H > HOOCCH2CH2COOH + 2H 



Acetic Acetic Succinic 



acid acid acid 



Synthesis of Succinic Acid by Dehydrogenative Coupling of Acetic Acid^^* 



Wieland and Sonderhoff'^" likewise suggested that the conversion of acetate 

 to succinate by yeast in the absence of oxaloacetate proceeded by a dehydro- 

 genative coupling. Moreover, Sonderhoff and Thomas, ^-^ employing 

 deuterioacetate, interpreted their results as evidence of the direct synthesis 

 of succinic acid; citric acid was also found to contain a large proportion of 

 deuterium. 



According to Bloch,^ proof of the synthesis of succinate by dehydro- 

 genative coupling would be conclusive only if the concentration of deute- 

 rium in succinate approached four deuterium atoms mstead of the two 

 atoms actually found. Although it is possible that several pathways for 

 the synthesis of succinate may be available, there is no proof that the re- 

 action does not involve exclusively synthesis via the tricarboxylic acid 

 cycle. This suggestion is strengthened by the fact that, in no case m which 

 succinate is synthesized is it the sole product; a-ketoglutarate and tri- 

 carboxylic acids also accumulate. Guzman-Barron and Ghiretti**' 

 suggested that the formation of succmate from acetate in Corynehacterium 

 creatinovorans (an aerobic, non-motile bacterium of the Mycobacteriaceae) , 

 Aerobacter aerogenes (from grains, plants, and. the intestmal tract of man 

 and animals, which uses citric acid as the sole source of carbon), Pseudo- 

 monas fluorescens (baker's yeast), and other molds may occur as the 

 result of the oxidative condensation of acetyl-CoA. 



(6) Acetopyruvic Acid. The condensation of acetic acid and of pyruvic 

 acid to yield five-carbon dicarboxylic acids can theoretically take place 

 by two pathways, give rise to acetopyruvic acid or to a-ketoglutaric 

 acid. When the carboxyl group of acetic acid condenses with the meth- 

 ylene group of pyruvic acid, acetopyruvic acid is formed. Krebs and 

 Johnson^^^ suggested the following equation for this S3Tithetic reaction: 



CH3-COiqH''£"H|CH2COCOOH > CHsCO-CHj-CO-COOH + HoO 



Acetic acid Pyruvic acid Acetopyruvic acid 



Synthesis of Acetopyruvic Acid"^ 



129 T. Thunberg, Skand. Arch. Physiol., 40, 1-91 (1920). 



130 H. Wieland and R. Sonderhoff, Ann., 499, 213-228 (1932). 



1" E. S. Guzman-Barron and F. Ghiretti, Biochim. Biophys. Acta, 12, 239-249 (1953). 

 i»2 H. A. Krebs and W. A. Johnson, Biochem. J., 31, 772-779 (1937). 



