120 III. OXIDATION AND METABOLISM 



topes that acetate is the primary degradation product, and that such ace- 

 tate may combine with oxaloacetate to be oxidized via the citric acid cycle, 

 one may postulate that the oxidation of fat in the peripheral tissues in the 

 absence of ketosis occurs because the acetate produced by oxidation is 

 readily removed and oxidized to CO2 and water. On the other hand, in tis- 

 sues like the liver (particularly during fasting) , there is less ability to oxidize 

 acetate via the citric acid cycle. The consequent accumulation of the ace- 

 tate results in the formation of acetone bodies. 



{4) The Metabolism of the Ketone Bodies 



a. Introduction. The most fruitful source of information concerning 

 the intermediary metabolism of fatty acids has been afforded by their close 

 relationship to the ketone bodies. This applies not only to the vast 

 amount of work reported prior to the employment of the isotopic technics, 

 but also to the investigations which have been carried out subsequently 

 with isotopes. 



The accumulation of the ketone bodies in the blood in abnormally large 

 amounts is referred to by the terms ketosis or ketonemia, while the presence 

 of these substances in the urine is designated by the terms ketonuria or 

 acetonuria. The ketone bodies, or acetone bodies, include the three sub- 

 stances, acetoacetic (or diacetic) acid, /S-hydroxybutyric acid, and acetone 

 which always occur in association. It is generally considered that aceto- 

 acetate is the primary product. It is in equilibrium with /3-hydroxybutyrate, 

 while acetone can be formed from it by decarboxylation. These relation- 

 ships are indicated below: 



H 



-H2 11 



CH3CCH2COOH ' CHa-CCHoCOOH > CH3COCH3 + CO2 



OH +H2 



/3-Hydroxybutyric Acetoacetic Acetone 



acid acid 



The Metabolic Interrelations of the Ketone Bodies 



It is generally believed that ketone bodies are compomids normally oc- 

 curring in the animal body. Under conditions in which carbohydrates are 

 present in the diet in normal amounts, only traces of these substances are 

 found in the blood, tissue fluids, and urine. However, when carbohydrate is 

 unavailable, as in fasting, when it cannot be utilized, as in diabetes, or 

 when the body is called upon to metabolize excessive amounts of fat, a 

 marked ketosis, with a concomitant ketonuria, may ensue. 



Substances which are convertible to the ketone bodies are referred to as 



