FAT METABOLISM 737 



What evidence have we that such a process actually occurs in the body? 

 If we compare the intake of oxygen with the output of carbon dioxide 

 in the respired air, we shall find that usually there is less of the latter; 

 that is to say, the respiratory quotient, as this ratio is called, is usually 

 less than unity. During the extensive conversion of carbohydrate into 

 fat, however, which occurs during the fall months in hibernating animals, 

 the R.Q. has been found to rise as high as 1.4. The great excess of 

 C0 2 - output over 2 - intake which such a quotient indicates conforms 

 with the above equation. 



The entire dissimilarity in chemical structure between the molecules 

 of fat and carbohydrate suggests that the primary step in the conversion 

 must be a thorough breakdown of the carbohydrate chain into compara- 

 tively simple molecules, from which the fat molecules are then recon- 

 structed and the unnecessary oxygen set free. The problem is to ascer- 

 tain the chemical structure of these simpler molecules and the manner 

 of their union into 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 lfi H 32 2 ; stearic, C 18 H 3G 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, undergoes only a partial oxidation when the metab- 

 bolism is upset, resulting in the production of various intermediary prod- 

 ucts. These accumulate 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 



