218 IV. CONVERSION OF FAT TO CARBOHYDRATE 



tion in the glycogen levels in the livers of rats fed butyrate in addition to 

 glucose over those in the group given glucose alone. Although the possi- 

 bility of a minimal transformation of butyrate to glucose could not be ab- 

 solutely ruled out in these latter experiments, it seems most logical to as- 

 sume that the increased glycogen which has been noted after the adminis- 

 tration of butyrate should be ascribed to a sparing action exerted by the 

 fatty acid on glycogenolysis, rather than to a glyconeogenesis from the 

 but3rrate molecule. Tidwell and Axelrod^^ were imable to correlate hyper- 

 glycemia in rats with the injection of acetoacetate. 



Another type of investigation which has been employed to follow pos- 

 sible interrelations of butyrate and carbohydrate is the use of isolated tis- 

 sues. Thus, Blixenkrone-M011er^^ presented evidence that glycogen syn- 

 thesis occurred when butyrate was artificially perfused through cat liver. 

 It was suggested that only 20% of the butyrate which disappeared was 

 changed to ketone bodies, while the balance was converted to sugar. Haar- 

 mann and Schroeder^^ also reported that several tissues, including the liver, 

 have the ability to transform butyrate to glucose. The following pathway 

 is suggested: butyric acid, crotonic acid, /3-hydroxybutyric acid, acetoacetic 

 acid, dihydroxybutyric acid, dihydroxycrotonic acid, diketobutyric acid, 

 methyl glyoxal, pjTuvic acid, lactic acid, sugar. The behavior of butyrate 

 in the case of cat liver differs from that observed by Bobbitt and DeueP' 

 with rat liver slices. In the latter case, although ketone bodies were formed 

 when liver slices from fasting rats were immersed in a butyrate medium, 

 the amount of ketones recoverable was less, and the quantity of butyrate 

 disappearing was greater when glycogen was also present in the medium. 

 The implication of this experiment is exactly the opposite of that reported 

 by Weil-Malherbe," who noted that kidney slices (but not liver slices) were 

 able to form additional reducing substances in a medium containing aceto- 

 acetate; it was later shown, ^* by the osazone test and by the fermentation 

 reaction, that the reducing substance was glucose. It was believed that 

 pyruvic acid acted as an intermediate. 



On the other hand, Stadie and associates'^ failed to confirm the latter in- 

 vestigation. They have likewise pointed out that, in the experiments of 

 Weil-Malherbe, "the excess of newly-formed fermentable substances, pre- 



=3 H. C. Tidwell and H. E. Axelrod, J. Biol. Chem., 172, 179-184 (1948). 

 " N. Blixenkrone-M0ller, Z. physiol. Chem., 252, 137-150 (1938). 

 " W. Haarmann and E. Schroeder, Biochem. Z., 296, 35-46 (1938). 

 »6 B. G. Bobbitt and H. J. Deuel, Jr., /. Biol. Chem., US, 1-9 (1942). 

 " H. Weil-Malherbe, Biochem. J., 32, 1033-1053 (1938). 



58 H. Weil-Malherbe, Biochem. J., 32, 2276-2282 (1938). 



59 W. C. Stadie, J. A. Zapp, Jr., and F. D. W. Lukens, J. Biol. Chem., 137, 63-74 

 (1941). 



