306 PHYSIOLOGICAL CHEMISTRY 



Of the acetone bodies, the acetoacetic acid is considered to be the 

 most important. This acid has its origin principally in fats, and to 

 a minor degree in certain amino acids resulting from protein cleavage. 

 It has been demonstrated that acetoacetic acid may be formed in 

 the body through the oxidation of butyric acid, and that the administra- 

 tion of fats containing butyrin to diabetics causes an increased produc- 

 tion of acetoacetic acid. Furthermore, it is believed that fatty acids 

 higher than butyric acid in the series also yield acetoacetic acid by 

 oxidation. In this change the oxidation occurs at the 0-carbon, 

 two carbon atoms at a time being involved. As soon as the oxidation 

 proceeds to the butyric acid stage this acid is transformed into aceto- 

 acetic acid. In diabetes the body either does not possess the normal 

 power of oxidizing acetoacetic acid or else this acid is produced in 

 excessive amount. At any rate, we find it in blood and urine in ab- 

 normal quantity. The relationship of acetoacetic acid to fatty acids 

 may be expressed as follows : 



CH 3 -CH 2 -CH 2 -CH 2 ;CH 2 -COOH 



Caproic acid 



lo 



CH 3 -CH 2 -CH 2 -COCH 2 -COOH 



fo 



CH 3 -CH 2 -CH 2 -COOH 



Butyric acid 



40 

 CH 8 -CO-CH 2 -COOH 



Acetoacetic add 



The jS-hydroxybutyric acid is formed from acetoacetic acid by 

 reduction. It was originally believed that this procedure was reversed 

 and that the acetoacetic acid was formed from the j3-hydroxybutyric 

 acid by oxidation. However, it has been shown that the introduction 

 of jS-hydroxybutyric acid into the body is not followed by an increased 

 acetoacetic acid formation, whereas, /3-hydroxybutyric acid is formed 

 when acetoacetic acid is introduced. Therefore, it seems clear that 

 the acetoacetic acid is the original substance from which the /3-hydroxy- 

 butyric acid is formed by a process of reduction. The relationship 

 between the acetone bodies may be indicated in this way: 



CH 3 -CO-CH 2 -COOH -> CH 3 -COCH 3 + CO 2 



Acetoacetic Acid Acetone 



I H (reduction) 

 CH 3 -CHOH-CH 2 -COOH 



0-hydroxybutyric acid 



In the normal body it is probable that the bulk of the acetoacetic 

 acid is oxidized to acetic acid and carbonic acid in turn and thence to 

 carbon dioxide and water, whereas, in the diabetic organism this does 



