740 METABOLISM 



We know practically nothing as to the conditions determining whether oxidation or 

 reduction shall predominate, but there are two significant facts that one should bear in 

 mind: (1) that a plentiful supply of oxygen is necessary for the oxidative process, and 

 (2) that the presence of readily oxidizable material in the liver (e.g., carbohydrates) 

 may determine the direction which the reaction shall take. It is commonly said that 

 fats burn in the fire of carbohydrates, and it may be that the undoubted diminution in 

 acidosis which occurs in diabetes when carbohydrate food is given is dependent upon the 

 directive influence which its combustion in the liver has on the above processes. But 

 we must be cautious not to transfer results obtained by experiments with minced liver 

 in judging of the reactions which occur during life. Provisionally, then, we must assume 

 either that /3-hydroxybutyric acid is a necessary stage in the oxidation of butyric acid 

 or that it is formed by reduction of acetoacetic acid, which is really the first step in 

 that process. 



Of course there is no evidence in the above experiments that the higher fatty acids 

 are also broken down by the removal of two C-atoms at a time, nor has it been possible 

 to detect any ketonic or /3-hydroxy derivatives of them in the animal body. We can only 

 reason from analogy that a similar process may occur, although some support is fur- 

 nished for such a view by the fact that ketonic fatty acids have been found in vegetable 

 organisms. 



What, then, it may be asked, is the relation of the desaturation of fatty acids which 

 we have seen occurs in the liver (and probably elsewhere) to the /3 oxidation? There 

 can be no doubt that both processes can occur in the animal body, indeed in the same 

 organ, e.g., the liver; and it is important to ascertain their relationship to each other. 

 The conclusion which would seem to conform best with the known facts is that the de- 

 saturation process occurs (in the liver) so as to break up the long fatty-acid chain into 

 smaller chains, which are then capable of /3 oxidation (in the tissues) ; desaturation may 

 be the process by which the molecule is rough hewn, and /3 oxidation that by which the 

 resulting pieces are finally split to their smallest pieces that is, to molecules of the size 

 of acetic acid, which are finally completely burnt to carbonic acid and water. 



The increase of iodine value observed by Leathes and his coworkers need not, as has 

 already been pointed out, necessarily indicate that new double linkages have been intro- 

 duced in the fatty-acid chain; it may merely indicate that structurally isomeric deriva- 

 tives which absorb iodine more readily have been formed. Direct evidence of desatura- 

 tion has, however, been offered by Hartley, who isolated the unsaturated fatty acids (by 

 dissolving the lead soaps in ether) from pig's liver and then proceeded to oxidize them 

 with alkaline permanganate. When the olein of the depot fat is thus treated at a low 

 temperature, two hydroxyl groups become attached where the double linkage existed 

 (forming dioxystearic acid), and when the mixture is now warmed, the molecule splits 

 into two at this place, forming two lower acids (pelargonic and azelaic) : 



(1) CH 3 -(CH 2 ) 7 CH:CH(CH 2 ) 7 COOH; 

 (oleic acid) 



OH OH 



/ / 



(2) CH 3 - (CH 2 ) 7 -CH- -CH (CH 2 ) 7 COOH; 



(dioxystearic acid) 



(3) CH 3 (CH 2 ) 7 COOH + COOH-(CH 2 ) 7 COOH. 



(pelargonic acid) (azelaic acid) 



We may conclude from this that the double linkage in the oleic acid of the depot fat 

 exists between the ninth and tenth C-atoms. But it is otherwise in the case of the un- 

 saturated acid from the liver (pig's), for under the above process of oxidation this 

 yielded caproic acid, which, since this acid has six C-atoms, would indicate that the 



