POLYCARBOXYLK' ACIDS 305 



olized by the liver to acetoacctic acid; it was found that 1.3 moles of 

 acetoacetate were formed per mole of triacetic acid, (/3,5-diketohexanoic 

 acid). On the other hand, kidney, muscle, and lung were unable to attack 

 the diketonic acid. The results are interpreted as offering support for the 

 multiple alternate oxidation theory, as far as liver is concerned, while they 

 exclude the validity of this concept in the peripheral organs. 



3. Polycarboxylic Acids 



(1) Dicarboxylic Acids 



a. Functions of the Dicarboxylic Acids. Although the dicarboxylic 

 acids are not important components of the food, and are not generally 

 considered as direct intermediates in fat utilization, two important func- 

 tions are now recognized. Thus, dicarboxylic acids form some of the 

 essential components of the tricarboxylic acid (or Krebs) cycle, which 

 assists in the oxidation of acetic acid and of carbohydrate intermediates; 

 dicarboxylic acids may normally also be formed, in some cases, as inter- 

 mediates in the breakdown of the fatty acids of moderate chain-length by 

 the so-called process of w-oxidation. 



(a) The Role of Dicarboxylic Acids in the Tricarboxylic Acid Cycle. The 

 successful functioning of the tricarboxylic acid cycle in activating the pro- 

 duction of energy is midoubtedly related to the ability of the dicarboxylic 

 acids to interchange, and to build up to the tricarboxylic acids, isocitric, 

 citric, and aconitic. Oxaloacetic acid, HOOC • CO ■ CHo • COOH, appears to 

 be the key acid in the fmictioning of the cycle. This acid is conjugated 

 with a two-carbon compound to yield, in turn, the six carbon acids, citric, 

 cis-aconitie, isocitric, and oxalosuccinic. a-Ketoglutaric acid, HOOC-- 

 CO • CH2 • CH2 • COOH, is formed next; the following members of this 

 cycle are, in succession, the four-carbon dicarboxylic acids, succinic (HO- 

 OC -CHs-CH,- COOH), fumaric (HOOC -CHiCH- COOH), and malic 

 (HOOC • CH2 • CHOH • COOH) ; malic acid is readily converted into oxalo- 

 acetic acid, and the cycle can be restarted. 



The discovery and recognition of this cycle as a method for promoting 

 the oxidation of carbohydrate and fat intermediates is largely due to the 

 work of Krebs^^ alone and with Johnson.^' However, somewhat earlier, 

 Annau el al.^^ and Stare and Baumann^^ had reported that the four-carbon 



" H. A. Kreb.s, Advances in Enzymol., 3, 191-252 (1943). 



" H. A. Krebs and W. A. Johnson, Enzymoloyia, 4, U8-156 (1937). 



■•* E. Annau, I. Banga, B. Gozsy, St. Huszak, K. Laki, B. Straub, and A. Szent- 

 Gyorgyi, Z. physiol. Chem., 236, 1-68 (1935); E. Annau, I. Banga, A. Blazso, V. Bruck- 

 ner, K. Laki, F. B. Straub, and A. Szent-Gyorgyi, Ihid., 2U, 105-152 (1936). 



« F. J. Stare and C. A. Baumann, Proc. Roy. Soc. London, B 121, 338-357 (1936). 



