222 IV. CONVERSION OF FAT TO CARBOHYDRATE 



the tagged carbon appeared in the urinary glucose during the first forty- 

 eight hours; about 14% of the isotopic carbon was found in the sugar iso- 

 lated during the first ninety-six hours. When the 1-C ^''-palmitic acid was 

 given, the C^^ was equally divided between the third and fourth carbons. 

 When palmitic acid-G-C^* was administered, only about 10% of the in- 

 jected carbons appeared on each of carbons 3 and 4, while the 80% balance 

 was equally distributed between carbons 1, 2, 5, and 6. 



According to Buchanan and Hastings,*^ Wood,^- and Bloch,^^ there is no 

 inconsistency in the fact that a substance like acetic acid can provide 

 carbon atoms for all the positions of the glucose molecule and still be un- 

 able to effect an increase in the glycogen level in the animal. Two dif- 

 ferent processes are involved. In the first case, the precursor affords a net 

 increase in the quantity of the substance formed, since the amount of the 

 precursor present is the limiting factor. This type of reaction can be 

 demonstrated by increased glycogen formation or by the exhibition of a 

 ketolytic effect. This is the classical concept of glycogenesis, and acetic acid 

 obviously does not fit into this category. 



In the second type of reaction, the precursor may be partly or wholly in- 

 corporated into the reaction product, but its presence is without effect on 

 the rate of formation of the new product. Acetic acid fits into this scheme 

 insofar as glycogen formation is concerned. Acetic acid alone cannot form 

 glucose or pyruvate, but only by becoming incorporated into the tricar- 

 boxylic (citric) acid cycle. As a result of this reaction, some of the acetic 

 acid carbons may be transformed into pyruvic acid, which is known to be, 

 without question, an obligatory intermediate in glucose formation. Thus, 

 in conditions of fasting, during which the level of activity of the tricarboxylic 

 acid cycle is at a low ebb, only a small amount of acetate becomes incor- 

 porated in citric acid, and it is largely lost as ketone bodies. On the other 

 hand, when ample carbohydrate is available, acetate is readily utilized 

 in citric acid synthesis, ketonuria disappears, and some of the acetate 

 carbon appears in glucose and glycogen. This reaction may occur not only 

 when large amounts of carbohydrate are available, with the result that an 

 increased glycogen deposition obtains, but also when the Krebs cycle is 

 operating at a low level and no change in net glycogen takes place in the 

 tissues. For a further discussion of the relationship of acetate to the Krebs 

 cycle, the reader is referred to the discussion of the relationship of carbo- 

 hydrate to ketonuria (see page 169). 



81 J. M. Buchanan and A. B. Hastings, Physiol. Revs., 26, 120-155 (1946). 

 8" H. G. Wood, Physiol. Revs., 26, 198-246 (1946). 



