FAT METABOLISM 709 



That higher fatty acids, such as caproic (C 6 H 12 O 2 ) and caprylic (C 8 H 16 O 2 ), have 

 actually been isolated from the products of this fermentation is a very significant fact, 

 and it is of interest to note that Leathes has sometimes found an increase in higher fatty 

 acids to occur during the aseptic incubation of liver pulp. Unfortunately, however, the 

 increase of fatty acid could not be shown to be affected by adding substances to the 

 liver which, according to the above equations, should yield fatty acid. 



The Method by Which the Fatty Acid is Broken Down. In the chemi- 

 cal laboratory, ordinary oxidizing agents attack the fatty-acid chain at the 

 C-atom next the carboxyl (COOH) group (the alpha C-atom). But 

 this can not occur in the animal body, because it would leave behind a 

 smaller chain containing an uneven number of C-atoms, and such chains 

 are never found present in the animal fats. On the contrary, the com- 

 moner fats all contain an even number of C-atoms ; thus : Butyric, C 4 H 8 2 ; 

 palmitic, C 1C H 32 2 ; stearic, C 18 H 3( .0 2 ; oleic, C 18 H 34 2 . 



The intermediary substances which are produced during the gradual 

 breakdown of the fatty-acid molecule in the normal animal are of a very 

 transitory character so much so indeed that it is impossible for any one 

 of them to accumulate in sufficient amount to permit of isolation, or even 

 detection, by chemical means. How then are we to identify the inter- 

 mediary products? This has been rendered possible by the discovery that, 

 when anything occurs to disturb the normal course of fat metabolism, as, 

 for example, when the tissues are deprived of carbohydrates (as in star- 

 vation or in severe diabetes), the oxidation of the fatty-acid chain stops 

 short when a chain of four C-atoms still remains unbroken. These last 

 four C-atoms seem to form a residue that is more resistant to oxidation 

 than the remainder of the fatty-acid molecule. It is a residue, therefore, 

 which is quite readily further oxidized to C0 2 and H 2 under normal con- 

 ditions, but which, although incapable of becoming completely oxidized 

 Avhen the metabolism is upset, does undergo a partial oxidation, result- 

 ing in the production of various intermediary products. These accumu- 

 late in the body in sufficient amount to overflow into the urine, from 

 which they can be isolated and identified. 



The fatty acid with 4 C-atoms is 'butyric, CH 3 CH 2 CH 2 COOH, and the 

 first oxidation product formed from it in the body seems to be fi-oxybuiy- 

 ric acid, CH 3 CHOHCH 2 COOH. This then becomes oxidized to form a 

 body having the formula CH 3 COCH 2 COOH, acetoacetic acid, which, on 

 further oxidation, readily yields CH 3 COCH 3 , or acetone. These sub- 

 stances (/?-oxybutyric acid, acetoacetic acid and acetone) appear in the 

 urine during carbohydrate starvation, as in diabetes. 



It might be objected, however, that a chemical process occurring under 

 abnormal conditions need not also occur in the normal animal. That it 

 probably does, hoAvever, is indicated by the results of the experiments 



