314 VII. ACIDS, AMIDES, ALDEHYDES AND HYDROCARBONS 



sugar excretion by phlorhizinized animals; this, of course, might possibly 

 be attributed to their nephropathic action. Mazza^^ brought forward the 

 direct proof that tissues can oxidize the dicarboxylic acids by demon- 

 strating this phenomenon in liver slices with the following acids: succinic 

 (C4); adipic (Ce); suberic (Cs); azelaic (Cg); sebacic (Cio); and hexane 

 dicarboxylic (Cie). Only glutaric acid (C5) was not attacked by liver 

 slices, while kidney slices did not break the latter acid down to an appre- 

 ciable extent. 



(2) Tricarboxylic Acids 



The metabolism of tricarboxylic acids is intimately bomid up with that 

 of the shorter-chain dicarboxylic acids through the Krebs cycle. Thus, 

 citric acid has been repeatedly proved to be a glucose former. Baer and 

 Blum^- demonstrated that an increase in glucose obtained when citric acid 

 was fed to a phlorhizinized dog. Greenwald^^ also reported that sodium 

 citrate augmented the glucose excretion, both in the case of phlorhizinized 

 dogs and in the diabetic human patient. MacKay, Carne, and Wick'"" 

 have demonstrated in an unequivocal manner that citric acid is as effective 

 as glucose in relieving the symptoms of hypoglycemia in albino rats; this 

 acid was also shown to fimction as a glycogenic agent, and to exert an 

 antiketogenic action. On the other hand, Fiirth and co-workers'"^ were 

 unable to demonstrate either a glycosuric or an antiketogenic effect on the 

 part of citric acid in the phlorhizinized dog; moreover, no increase in liver 

 glycogen could be demonstrated in rats after feeding them citric acid. 

 Although the majority of experimental data point to the conversion of 

 citric acid to glucose, the single negative report makes one cautious about 

 interpreting such data. Because of the interrelations of the several four- 

 carbon dicarboxylic acids, a-ketoglutaric acid and the several six-carbon 

 dicarboxylic acids other than citrate in the tricarboxylic acid cycle, it 

 would seem quite probable that they must all be considered as glucose 

 formers. The finding by Orten and Smith^''^ that the injection of all the 

 compounds in the citric acid cycle increased the citrate excretion would 

 seem to support this thesis. Krebs et al.'^^^ obtained a similar result, and 

 demonstrated that the excretion of a-ketoglutarate was also augmented 

 when any components of the citric acid cycle were administered. 



S8 F. P. Mazza, Arch. sci. biol. {Italy), 22, 307-326 (1936). 



S3 I. Greenwald, /. Biol. Chem., 18, 115-121 (1914). 



'«o E. M. MacKay, H. O. Carne, and A. N. Wick, J. Biol. Chem., 133, 59-65 (1940). 

 i«i O. Fiirth, H. Minnibeck, and E. Edel, Biochem. Z., 269, 379-396 (1934). 

 102 J. M. Orten and A. H. Smith, J. Biol. Chem., 117, 555-567 (1937). 

 i»3 H. A. Krebs, E. Salvin, and W. A. Johnson, Biochem. J., 32, 113-117 (1938). 



