278 VI. ACETIC, FORMIC, AND PROPIONIC ACIDS 



acid is another possible tricarboxylic acid which may be an intermediate, 

 since the oxalosuccinic acid — »- isocitric acid change is a reversible one. 



(5) Resume of the Metabolism of Acetic Acid 



It has long been recognized that acetic acid is readily metabolized by the 

 animal, but the pathway of this degradation remained an enigma mitil the 

 advent of the radioisotope technic. Lusk^^- reported that the dog 

 apparently could oxidize large amounts of acetic acid, since the acid which 

 was administered disappeared; it was without effect in changing the 

 C02-combining powder of the blood. It is not converted to "extra sugar" 

 in the phlorhizmized dog,^^"'"' and the amount of glycogen is not increased 

 by its administration. However, there is some evidence, based upon 

 tracer studies, that acetate can be incorporated into the glycogen stores 

 of an animal without increasmg the total amount of this polysaccharide. ^^^-^'^ 



It was formerly believed that acetate was oxidized directly to carbon 

 dioxide and water. However, no one has been able to prove any inter- 

 mediate stages in this oxidation. Thus, Kleinzeller^^^ reported that 

 neither glycohc acid, glyoxyhc acid, nor glycine can be considered as an 

 intermediate. Guzman-Barron and Ghiretti^*^ demonstrated that enzymes 

 are present in microorganisms which are active in the synthesis of citric 

 acid and in the oxidation of isocitric acid. They found the enzymes in 

 the bacillus from plants and animals, Aerobacter aerogenes, in the animal 

 and plant pathogen, Corynebacterium creatinovorans, in black bread mold, 

 Rhizopus nigricans, and in reactions in which the oxidation of acetate had 

 been presumed to occur via glycolic acid, as is the case with the dry wood- 

 rot molds, Merulius tremellosus and M. niveus. The present concept is 

 that acetic acid is oxidized by being incorporated into the tricarboxylic 

 acid cycle. There is some disagreement as to whether it combines with 

 oxaloacetate as the acetate or as the acetoacetate group. However, it is 

 known that acetate must be in an active form to effect the condensation; 

 this requires the intervention of an enzyme, as well as of a coenzyme, 

 which is known as Coenzyme A. Elhott and Kalnitsky^^^ demonstrated 

 that, when acetate is oxidized by homogenates of rabbit kidney cortex, 

 Mg++ or Mn++, inorganic phosphate, and ATP, as well as oxaloacetate 

 and pantothenate, are also required for the oxidation. The oxidation 

 of acetate was found to be inhibited by malonate, arsenite, iodoacetate, 

 and fiuoroacetate. 



1" G. Lusk, /. Biol. Chem., 49, 453-478 (1921). 



1" A. Kleinzeller, Biochem. J., 37, 674-677 (1943). 



J" W. B. Elliott and G. Kalnitsky, /. Biol, Chem., 186, 477-486 (1950). 



