TRANSFORMATION OF FATTY ACIDS 219 



siimabl}'' carbohydrate, .... formed from acetoacetate over control slices 

 without acetoa(;etate was (by our calculation) 4.0 ±2.1 millimoles of wet 

 tissue per g. per hour." This is only 8% of that derived from pyruvate, and 

 scarcely differs from 0. Finally, since no lactic acid determinations were 

 made, it is possible that lactate may be the source of the new carbohydrate. 

 Stadie et ai.^^ demonstrated that a considerable amount of fermentable car- 

 bohydrate can be s>aithesized by liver slices of diabetic cats from l (dextro)- 

 lactic acid. 



Another result which contradicts the view that butyric acid is converted 

 to carbohydrate is the antagonism which has repeatedly been demonstrated 

 between the level of urinary ketones and the quantity of carbohydrate in- 

 gested. The administration of butyric acid, either in the form of the ethyl 

 ester or as the sodium salt, to fasting rats, always results in the excretion of 

 ketone bodies in the urine. "•^^•®''~" This ketonuria can be prevented by the 

 administration of glucose in an amount as small as 25 mg. per 100 sq. cm. 

 of surface area, twice daily. Were butyrate normally transformed to glu- 

 cose in any appreciable amounts under these conditions, not only would it 

 no longer be available for the production of ketonuria, but it would tend to 

 remo^'e any existing ketonuria. This argument is supported by the keto- 

 genic effect of related four-carbon acids. Thus, a ketonuria of similar de- 

 gree occurs following the administration of acetoacetate^^ -^^ to fasting rats, 

 as well as after the feeding of /3-hydroxybutyrate'"' or crotonate®"-'''' to such 

 animals. The ketonuria in these latter cases is likewise prevented by the 

 administration of glucose.*'''''' 



c. Long-Chain Acids and Fats as Possible Sources of Carbohydrate. 

 The acids longer than butyric having an even number of carbon atoms are 

 also not glycogenic. Thus, completely negative results were noted, insofar 

 as liver glycogen is concerned, when the sodium salt of caprylic acid was 

 fg(^ 21,33 Qj. -^vhen the ethyl esters of caproic, caprylic, capric, mj^ristic, or 



«« H. J. Deuel, Jr., C. E. Calbert, L. Anisfeld, H. McKeehan, and H. D. Blunden, 

 Food Research, 19, 13-19 (1954). 



" J. S. Butts and R. O. Sinnhuber, /. Biol. Chem., 139, 963-969 (1941). 



" J. S. Butts, ]\I. S. Dunn, and L. F. Hallman, /. Biol. Chtm., 123, 711-718 (1938). 



" C. Johnston and H. J. Deuel, Jr., J. Biol. Chem., 149, 117-124 (1943). 



" C. E. Vaniman and H. J. Deuel, Jr., /. Biol. Chem., 152, 565-570 (1944). 



65 J. S. Butts, H. Blunden, and M. S. Dunn, /. Biol. Chem., 119, 247-255 (1937). 



•6 J. S. Butts, H. Blunden, and M. S. Dunn, /. Biol. Chem., 124, 709-714 (1938). 



6' J. S. Butts and R. O. Sinnhuber, /. Biol. Chem., I40, 597-602 (1941). 



6« J. S. Butts and H. J. Deuel, Jr., /. Biol. Chem., 100, 415-428 (1933). 



«9 J. S. Butts, /. Biol. Chem., 105, 87-96 (1934). 



'" H. D. Blunden, The Intermediary Metabolism of Butyric Acid as Determined from 

 the Physiological Behavior of the Various Four-Carbon Acids. Dissertation, Univ. South- 

 ern California, Dept. Biochem. Nutrition, 1938. 



