TRANSFORMATION OF FATTY ACIDS 217 



glucose-former,^^ this would constitute a possible pathway for the biosyn- 

 thesis of glucose. However, there is a preponderance of evidence that acetic 

 acid does not serve as a source of carbohydrate in the animal body, insofar 

 as can be demonstrated by quantitative experiments. 



b. Butyric Acid as a Possible Source of Carbohydrate. Butyric acid is 

 regarded by most workers in the fat field as an intermediate in fat oxida- 

 tion ; therefore, any demonstration of the transformation of this metabolite 

 to sugar should be accepted as direct proof of the fatty acid — carbohydrate 

 transformation. Although there is no convincing proof of the formation 

 of butyric acid in the course of fat catabolism, there is no question that the 

 closely related "ketone bodies" originate directly from the longer-chain 

 fatty acids ha\dng an even number of carbon atoms.'* In fact, butyrate 

 has been regularly employed by the Deuel group as the sodium salt to pro- 

 duce exogenous ketonuria in rats. In the case of fasting female rats, the 

 transformation of butyrate to acetone bodies is greater than 50% of that 

 ingested.*' 



The data are quite unaiiimous in indicating the failure of butyrate to in- 

 fluence the level of tissue carbohj^drate quantitatively when given to fasted 

 animals. Thus, when butyrate was fed as the sodium salt-' •''•'''' or as its 

 ethyl ester, '^ to rats, little or no glycogen formation could be observed in the 

 liver of fasting animals. On the other hand, there are several reports that 

 some additional glycogen formation occurs in non-fasted animals when bu- 

 tyrate is fed concomitantly with carbohydrate, as compared with that which 

 was observed when the carbohydrate was given alone. *''*°'*^ In all cases, 

 the increased amounts of glycogen were small; for example, in the experi- 

 ments of Buchanan et al}^ in which butyric acid-l-C* was employed, the 

 butyrate changed to glycogen comprised less than 5% of the butyrate ab- 

 sorbed. Moreover, Dziewiatkowski and Lewis^° do not interpret their in- 

 creased glycogen after butyrate as necessarily an indication of the change of 

 fat to carbohydrate; instead of this, they suggest the possibility that "the 

 butyrate is oxidized readily and thus protects the liver glycogen so that 

 glycogenolysis is diminished . . . ." In a further study of the effect of 

 butyrate feeding in the case of fasted rats or of those simultaneously fed 

 glucose, Deuel and co-workers*^ Avere unable to demonstrate any augmenta- 



« A. I. Ringer, E. M. Frankel, and L. Jonas, /. Biol. Chem., 14, 5.39-550 (1913). 



" H. J. Deuel, Jr., L. F. Hallman, and S. Murra^v, /. Biol. Chem., 124, 385-393 (1938). 



60 D. D. Dziewiatkowski and H. B. Lewis, /. Biol. Chem., 153, 49-52 (1944). 



" J. M. Buchanan, A. B. Hastings, and F. B. Nesbett, J. Biol. Chem., 150, 413-425 

 (1943). 



'* H. J. Deuel, Jr., C. Johnston, M. G. Morehouse, H. S. Rollman, and R. J. Winzler, 

 J. Biol. Chem., 157, 135-140 (1945). 



