176 III. OXIDATION AND METABOLISM 



tration of an amount of glucose sufficient to replace only an insignificant 

 amount of the fat being catabolized. It is difficult to present decisive 

 evidence that this carbohydrate effect is being exerted only on that portion 

 of the fat being metabolized in the liver which is the precursor of the 

 ketone bodies. However, in the case of exogenous ketonuria, one is not 

 faced with any similar difficulty in determining the amount of ketogenic 

 material being metabolized. Thus, when a given amount of sodium 

 acetoacetate, sodium butyrate, or sodium caproate is fed, it cannot be 

 stored or withheld, but it must be metabolized, resulting in the production 

 of acetone bodies or, in case ketolytic material is available, converted to 

 CO2 and H2O. If the metabolism of acetoacetic acid or of other ketogenic 

 acids were not influenced by D-glucose, or if it were used in preference to 

 D-glucose, then its elimination should not be changed, after sugar feeding, 

 from that recorded in fasting. On the other hand, if D-glucose is preferen- 

 tially oxidized, then the proportion of ketone bodies should be increased 

 when glucose is administered. Just the opposite effect has been con- 

 sistently observed. 



There is considerable evidence that acetoacetate, /3-hydroxy butyrate, 

 butyrate, and caproate cannot be stored in the animal body. Thus, the 

 injection of ,S-hydroxybutyrate into fasting or fed nephrectomized rats 

 or dogs is followed by its rapid disappearance from the blood and the 

 tissues. ^'^^""'^ Butyrate"^ or caproate"^ is given as the triglyceride, it is not 

 stored in detectable amounts. The fact that D2O is rapidly excreted in 

 the urine after the feeding of deuteriotributyrin^^" would seem to indicate 

 that it is rapidly metabolized and not directly built into long-chains acids. 

 It is thus evident, in the tests with exogenous ketonuria, that ketogenic 

 acids must be metabolized whether or not glucose is available. When 

 glucose is present, these acids are no longer eliminated as ketone bodies, 

 but are presmnably broken down to CO2 and H2O. If glucose effects this 

 change, the most logical explanation is that it does so by ketolysis. 



The proponents of the antiketogenesis theory accept the fact that, in 

 exogenous ketonuria, the administration of glucose is followed by the 

 disappearance of the ketonuria. However, these results are interpreted 



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 680 M. G. Morehouse, J. Biol. Chem., 155, 33-38 (1944). 



