TRANSFORMATION OF FATTY ACIDS 221 



tions are quite similar to those of fat feeding; there is an initial decrease in 

 nitrogen excretion, but after several days this excretion frequently exceeds 

 the prefasting level, until the more labile deposits have been exhausted." 



{2) Experiments Involving the Use of Isotopes 



From a quantitative standpoint, there is no convincing evidence that 

 acetic acid may be converted to glycogen or to glucose. Thus, acetic acid 

 does not satisfy the classical concept of this transformation, since neither 

 the deposition of glycogen in the liver of a fasting animal nor the glycosuria 

 of the diabetic animal is enhanced. However, Lorber, Lifson, and Wood^^ 

 demonstrated, by isotope experiments, that acetic acid can furnish the 

 carbon atoms for all positions in the glucose molecule. Lifson et al?^ like- 

 wise proved that the appearance of C^ ^-labeled glycogen in the liver of the 

 rat after C^Mabeled butyrate or acetate had been given represented an ac- 

 tual transfer of the fatty acid carbon to glycogen and was not merely 

 incorporated in the carbohydrate molecule by the combination of the car- 

 bohydrate precursor with labeled carbon dioxide. In a study in which 

 octanoate labeled with C^^ and C^"* was fed in conjunction with glucose to 

 fasted rats, the distribution of the isotope was consistent with the trans- 

 formation of 2-C fragments to glucose.^'' There was some evidence that the 

 last two carbons of the octanoate molecule are less readily convertible to 

 glycogen than are the first six carbons. 



Further evidence that fatty acid carbons may become incorporated into 

 glucose has been reported by the Chaikoff group. Thus, Strisower, Chai- 

 koff, and Weinman ^^ reported the presence of C^^-glucose in the urine of al- 

 loxan-diabetic rats after feeding labeled palmitic acid ; from 3 to 6% of the 

 injected palmitic acid-6-C^^ was recovered in the urme during the first 

 twenty-four hours. On the basis of the known rate of glucose turnover, 

 Strisower et al.^^ estimated that 6 to 12% of the injected palmitate was 

 transformed into glucose. It was calculated that from 1.6 to 2.9% of the 

 injected palmitic acid-6-C'^ was present in extracellular glucose in the dia- 

 betic rat, and 0.5 to 0.9% in the normal rat, one hour after injection. Ac- 

 cording to Abraham, Chaikoff, and Hassid,^' when palmitic acid-l-C^^ or 

 palmitic acid-6-C^^ was injected into diabetic dogs, approximately 6% of 



" H. J. Deuel, Jr., and M. Gulick, /. Biol. Chem., 96, 25-34 (1932). 

 78 V. Lorber, X. Lifson, and H. G. Wood, J. Biol. Chem., 161, 411-412 (1945). 

 " N. Lifson, V. Ix>rber, W. Sakami, and H. G. Wood, /. Biol. Chem., 176, 1263- 

 1284(1948). 



80 V. Lorber, M. Cook, and J. Meyer, J. Biol. Chem., 181, 475-479 (1949). 



