TRANSFORMATION OF FATTY ACIDS 215 



behavior of the simplest representative of the odd-numbered fatty acids, 

 namely formic acid, which is atj^pical, has only recently been understood. 

 The metabolism of this compound is described hi Chapter VI. 



Although the evidence is unequivocal that the odd-immbered fatty acids 

 containing from three to eleven carbons are converted to glycogen (prob- 

 ably to the same extent to which they are converted to propionic acid) when 

 they are fed as such or as their triglycerides, one should recognize that these 

 compounds are not physiologic, and that they do not occur in animal or 

 vegetable fats. The conversion of these compounds to glucose cannot be 

 construed as affording evidence of the formation of carbohydrate from 

 natural fats. 



3. The Transformation of Fatty Acids with Even-Numbered 

 Carbons to Carbohydrate 



Prior to the advent of isotopes, there was no convincing evidence that 

 the even-chain fatty acids could give rise to carbohydrate in the animal 

 body. Thus, it had been demonstrated that, with the exception of acetic 

 acid, the administration of e\'en-numbered fatty acids to fasting rats uni- 

 formty resulted in ketonuria,^^'^^ while it has been repeatedly demonstrated 

 that substances which give rise to carbohydrates are not only non-keto- 

 genic but actually comiteract an existing ketonuria. 



(1) Experiments Not Involving the Use of Isotopes 



a. Acetic Acid as a Possible Source of Carbohydrate. According to the 

 jS-oxidation theory, acetic acid is the two-carbon fragment split off when 

 long-chain fatty acids are metabolized. This supposition has been sup- 

 ported by the recent investigations in which isotopically-labeled fatty 

 acids were employed. Although, as will be reported later, acetic acid can 

 be shown to become incorporated into carbohydrate, there is considerable 

 evidence from a quantitative standpoint that acetate cannot alter the total 

 stores of carbohydrate in the animal body. 



In the first place, Stadie and associates'* were unable to obtain any evi- 

 dence of the presence of acetic acid or of any other steam-distillable fatty 

 acids in the liver slices of depancreatized cats. According to Stadie et 

 al.,^^ there were no experimental data in the literature previous to 1941 to 



3« J. S. Butts, C. H. Cutler, L. Hallman, and H. J. Deuel, Jr., J. Biol. Chem., 109, 

 597-613(1935). 



" H. J. Deuel. Jr., L. F. Hallman, J. S. Butts, and S. Murray, /. Biol. Chem., 116, 

 621-639 (1936). 



38 W. C. Stadie, J. k. Zapp, Jr., and F. D. W. Lukens, ./. Biol. Chem., 137, 75-87 

 (1941). 



