172 III. OXIDATION AND METABOLISM 



case, acetate formed citrate more readily than acetoacetate, it was believed 

 that acetate must be formed from acetoacetate before condensation with 

 oxaloacetate takes place. 



Because of the importance of CoA in effecting the incorporation of the 

 C2 unit into the tricarboxylic acid cycle,^^^ one would expect that this con- 

 densation would be depressed in pantothenic acid deficiency. Thus, 

 Olson et al}^^ found that the condensation of acetate proceeds at a markedly 

 subnormal rate in homogenized heart ventricle from pantothenic acid- 

 deficient ducklings. Cheldelin and co-workers^^^ reported that the oxida- 

 tion of caproate and butyrate by rats deficient in pantothenic acid was 

 less than one-half of that of control animals. Moreover, pantothenic 

 acid deficiency symptoms were found to be accentuated on a high-fat 

 diet.^^« 



Beatty and West ^" have shown that most of the substances related to 

 the tricarboxylic acid cycle are ketolytic. Thus, oxaloacetic acid and its 

 precursors (succinic, malic, a-ketoglutaric, aspartic, glutamic, and cis- 

 aconitic acids and alanine) were all able to reduce an exogenous ketonuria 

 produced by the administration of sodium butyrate. These results are 

 regarded as additional evidence supporting the operation of the Krebs 

 cycle in the animal and favoring the theory of fatty acid oxidation via 

 the tricarboxylic cycle. Ketosis results from a lack of oxaloacetic acid. 



c'. The Specific Effect of Glucose and of Glucose Precursors on Keto- 

 nuria: If antiketogenesis is the correct explanation for the depressing effect 

 of carbohydrate on ketonuria, then any substance capable of oxidation 

 in the body should cause the disappearance of the ketone bodies, irrespec- 

 tive of whether or not the substance in question gives rise to carbohydrate. 



However, the ability of substances to reduce either exogenous or en- 

 dogenous ketonuria is limited to those compounds, which are capable of 

 forming liver glycogen or of producing "extra sugar" when administered 

 to phlorhizinized or depancreatized dogs. Thus, in addition to D-glucose, 

 which has repeatedly been used as a standard for comparison in such 

 studies,22. 307, 324, 329, 340, 350.558-566 D-galactose, 350.387,566 D-fructose,^^^ lactose,^" 



6" R. E. Olson, E. G. Hirsch, H. Richards, and F. J. Stare, Arch. Biochem., 22, 480-482 

 (1949). 



«6 V. H. Cheldelin, A. P. Nygaard, C. M. Hale, and T. E. King, /. Am. Chem. Soc, 73, 

 5004-5005 (1951). 



656 W. D. Lotspeich, Proc. Soc. Exptl. Biol. Med., 73, 85-87 (1950). 



6" C. H. Beatty and E. S. West, /. Biol. Chem., 190, 603-610 (1951). 



5M H. J. Deuel, Jr., L. F. Hallman, S. Murray, and J. H. Hilliard, J. Biol. Chem., 125, 

 79-84 (1938). 



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



6«> C. E. Vaniman and H. J. Deuel, Jr., J. Biol. Chem., 152, 565-570 (1944). 



