FORMIC ACID AND FORMATE METABOLISM 279 



Although citric acid and related compounds have been shown to be 

 formed from acetate in yeast/-^ as well as in such isolated tissues as 

 kidney, ^^° the intermediates have not been proved in the intact animal. 

 However, Rittenberg and Bloch^^* demonstrated that labeled glutamic 

 acid (HOOC • CHCNHs) • CH2 • CH2 • COOH) , and aspartic acid (HOOC • CH- 

 (XH2) • CH2 • COOH), can be isolated from the liver proteins of rats and mice 

 after the feeding of C^Mabeled acetate. It is suggested that these com- 

 pounds originate from a-ketoglutarate and from a four-carbon dicarboxylic 

 acid with which the amino acids are in equilibrium. This should constitute 

 adequate proof of the operation of the tricarboxyhc cycle in the intact 

 animal. 



In addition to the incorporation of acetic acid into the components of the 

 tricarboxylic acid cycle, as occurs in oxidation, acetate readily disappears 

 from the tissues by becoming incorporated into many other new com- 

 pomids. Thus, it serves in the synthesis of fatty acids, cholesterol, proto- 

 porphyrin, uric acid, acetoacetate, and, to a Hmited extent, of glycogen. 

 Moreover, acetate maj^ be used to combine with amino groups to form 

 the acetylated compounds. 



Acetate is being continually formed by oxidation of fatty acids, amino 

 acids, and p>TU\dc acid (under certain specific conditions). Despite its 

 contmued production, it can be detected m the tissues only in traces. 

 Presumably, the failure to detect acetic acid is related to its rapid utilization 

 in one of the various metabolic pathways available for it. 



2. Formic Acid and Formate Metabolism 



(1) Introduction 



Little was kno^^^l of the participation of formic acid in metabolic proc- 

 esses prior to the advent of the isotope technic. In 1930, and agam 

 later, Edlbacher and co-workers^^^'" demonstrated that a molecule of 

 formic acid, together with one of glutamic acid and two of ammonia, were 

 formed when histidine was broken do^^^l by the enzyme, histidase. This 

 reaction was the only one in which formate was kno\ni to occur until the 

 fuidings of Sonne et al.^^^ in 1948. These workers studied the utilization of 

 acetate in ureide formation, and suggested that acetate is the biologic 

 som'ce of the ureide carbon, and that formate is either an intermediate or 

 may readily be converted into an intermediate of this reaction. 



1" D. Rittenberg and K. Bloch, /. Biol. Chem., 157, 749-750 (1945). 

 156 S. Edlbacher and J. Kraus, Z. physiol. Chem., 191, 225-242 (1930); 195, 267-272 

 (1931). 



1" S. Edlbacher and S. Neber, Z. phi/siol. Chem., 224, 261-272 (1934). 



'*8 J. C. Sonne, J. M. Buchanan, and A. M. Delhiva, /. Biol. Chem., 173, 69-79 (1948). 



