/Z III. OXIDATION AND METABOLISM 



ably involves their hydrolysis to fatty acids and glycerol. As mentioned 

 earlier, the metabolism of glycerol is apparently the same as that of glucose. 

 On the other hand, the oxidation of fatty acids is quite specific, and repre- 

 sents true fat oxidation. 



Although the different hypotheses for fat oxidation vary, they are not 

 necessarily mutually exclusive. It is possible that the several types of 

 reactions upon which the theories are based may occur concomitantly, 

 and that no single explanation will include all of the different reactions 

 which are possible in the degradation of fatty acids. 



a. i8-Oxidation Theory. According to the /S-oxidation theory, fatty acids 

 are oxidized on the carbon atom-3 (|8-carbon), which results in the forma- 

 tion of a (S-keto acid. Following this, a split occurs in the molecule, with 

 the result that an acetic acid molecule originates, and an acid remains 

 which has two less carbon atoms than the original acid. This process is 

 repeated until the long-chain acid is shortened to butyric acid, propionic 

 acid (in the case of odd-chain acids) or to acetic acid. Butyric acid may be 

 oxidized directly to acetoacetate and be excreted as such if the host is 

 fasting or is diabetic. On the other hand, acetic acid may be the terminal 

 compound in a normal animal, and this can then be utilized for energy via 

 the Krebs cycle. Under conditions of fasting or diabetes, acetic acid may 

 be rebuilt to acetoacetic acid, after which it will be partially or wholly 

 excreted in the urine as a component of the ketone bodies. Odd- chain 

 fatty acids are not ordinarily found as components of natural fats; how- 

 ever, when they are administered, they are broken down to propionic acid. 

 This latter acid is then converted to sugar; the resulting compound subse- 

 quently follows the usual paths of metabolism of the glucose molecule. 



The first experimental evidence of the phenomenon of /3-oxidation in 

 fatty acids was adduced in the classical experiments of Knoop'* in 1905. 

 Prior to this time, the nature of the intermediate compounds of fatty 

 acids could not be ascertained, inasmuch as the acid under study was com- 

 pletely oxidized, or was excreted unchanged. Knoop conceived the 

 idea of coupling the acid residue with a benzene group, since under these 

 conditions an incombustible residue remained which was excreted in the 

 urine. 



It had long been known that, after benzoic acid was given, it was de- 

 toxicated by conjugation with glycine, and that the resulting hippuric acid 

 was excreted in the urine as sho\\Ti on the next page : 



4 F. Knoop, Beitr. chem. Physiol. Pathol, 6, 150-162 (1905). 



