310 VII. ACIDS, AMIDES, ALDEHYDES AND HYDROCARBONS 



reported that, when a large dose (17.5 g.) was given to a dog weighing 24.8 

 kg., and the animal was sacrificed 90 minutes thereafter, the dicarboxylic 

 acid was largely utilized. For example, only 4.43 g. of the 17.5 g. injected 

 could be accounted for. This was isolated as follows: urine, 1.66 g. ; 

 blood, 1.38 g. ; total muscle, 1.05 g. ; liver, 0.17 g., and the balance of the 

 succinate widely distributed in a number of tissues. 



There is also considerable evidence that succinic acid is convertible to 

 glucose. Thus, Ringer et al.p and MacKay and Barnes''^ reported that 

 succinic acid yields glucose in the phlorhizinized dog. Moreover, this di- 

 carboxylic acid forms liver glycogen,^"*"" although Kutscher and Krab- 

 benhoft^^ concluded that C4 dicarboxylic acids in general do not increase 

 the glycogen formation. Succinic acid is also antiketogenic.'^^ ~''^ The 

 only conflicting evidence is that of Deuel, Murray, and Hallman,^^ who' 

 were unable to demonstrate any ketolytic effect comparable to that of 

 glucose. It is possible that the negative results obtained with succinate 

 in the latter tests may be attributed to the fact that the dicarboxylic acid 

 was fed as its sodium salt. If succinate were oxidized, sodium bicarbonate 

 would remain, producing an appreciable ketonuria.^" 



(c) Dicarboxylic Acids Having More Than Four Carbons. Although a- 



ketoglutaric acid is a most important component of the tricarboxylic acid 



cycle, glutaric acid has an independent fate. In the case of the dog, it 



appears to be completely oxidized^^ (apparently by the tricarboxylic acid 



cycle) ; on the other hand, Rose^^ reported that it is nephrotoxic for the 

 rabbit.«i-«2 



Adipic acid can be recovered in the urine of rabbits,^^ dogs,^^ and man,^^ 

 to the extent of 50 to 60% of that administered, when it is given orally 

 or parenterally. It also appears in small amounts in the urine after the 



^2 A. I. Ringer, E. M. Frankel, and L. Jonas, /. Biol. Chem., I4, 539-546 (1913). 



" E. M. MacKav and R. H. Barnes, Proc. Soc. Exptl. Biol. Med., 38, 417-419 (1938). 



7* A. P. Ponsford and I. Smedlev-MacLean, Biochem. J., 26, 1340-1344 (1932). 



'5 E. M. MacKay, J. W. Sherrill, and R. H. Barnes, J. Clin. Invest., 18, 301-305 (1939). 



'« R. Stohr, Klin. Wochschr., 17, 1663-1664 (1938). 



" W. Kutscher and F. Krabbenhoft, Z. physiol. Chem., 282, 54-60 (1947). 



'8 A. Kordnyi and A. Szent-Gyorgvi, Orvosi Heitlap, 81, 615-618 (1937); Chem. 

 Abst.,31, 6335 (1937). 



" H. J. Deuel, Jr., S. Murray, and L. Hallman, Proc. Soc. Exptl. Biol. Med., 37, 413- 

 414(1937). 



80 J. S. Butts, H. J. Deuel, Jr., and L. Hallman, Proc. Soc. Exptl. Biol. Med., 32, 898- 

 899(1935). 



81 W. C. Rose, J. Pharmacol. Exptl. Therap., 24, 123-146, 147-158 (1924). 



82 W. C. Rose, C. J. Weber, R. C. Corley, and R. W. Jackson, J. Pharmacol. Exptl. 

 Therap., 25, 59-64 (1925); W. C. Rose, and P. S. Dimmitt, Ibid., 25, 65-73 (1925). 



83 y. Mori, /. Biol. Chem., 35, 341-351 (1918). 



