554 AliM)RMAIATn:i< IS METABOLISM 



mind that the evidence of their low toxicity is based on short time 

 experimental intoxications, and that they may be found to be much 

 more toxic than is generally assumed when they are allowed to act 

 for many days and weeks on the nervous tissues, as they do in dia- 

 betes. That is, the experimental evidence concerning the toxicity of 

 the acetone bodies has not been obtained under conditions comparable 

 to those of diabetic acidosis. 



Origin of the Acetone Bodies. — The chemical nature of the acetone 

 bodies is such that they mijiht readily be produced from any or all of 

 the three classes of foodstuffs. 



They might be derived from carhohydrates, as is the closely related 

 lactic acid, but we know that this is not the usual source. On the 

 contrary, administration of a proper amount of carbohydrates under 

 certain conditions may cause the acids to disappear from the urine, 

 and acetone bodies may be eliminated in large quantities while the 

 patient is on a diet almost free from carbohydrates. Carbohydrates 

 are, indeed, the most active agents in preventing the formation of 

 these ketone bodies, i. e., they are antiketogenic.*' 



They might readily be formed from proteins through splitting out 

 of the NH2 group from the amino-acids ; indeed the amino-aeids 

 are generally considered as a source of the acetone bodies,*^ par- 

 ticularly because, whenever there is considerable pathological break- 

 ing-down of proteins, these bodies, especially acetone, may appear in 

 the urine ; e. g., during absorption of exudates, in carcinoma, and in 

 starvation or other conditions with great wasting of the tissues. 

 Dakin ^* has shown that only leucine, histidine. phenylalanine and 

 tyrosine yield diacetic acid when perfused through the liver, while 

 most of the other animo-acids are able to yield sugar in diabetic ani- 

 mals, and hence are antiketogenic. 



On the other hand, the amount of acids sometimes found in the 

 urine seems to be greater than can be explained by the protein de- 

 struction that occurs (Magnus-Lev^O,'*^ and in diabetes it is often ob- 

 served that feeding of fats and fatty acids increases the output of 

 acetone bodies, and hence it is evident that acetone bodies may be de- 

 rived from the fats. /?-oxybut}Tic acid can be readily produced from 

 fatty acids, especially, of course, from butyric acid, and we usually 

 observe an increase in the acetone excretion in a diabetic given large 

 quantities of butter. Other higher fatty acids are also found to cause 

 increased acetone excretion. 



41 Cnnceriiiii<r antiketofionosis see Woodvatt, Jour. Amor. ]\ro(l. Assoc, 1910 

 (.55), 210!). 



■»■■! Krnhdeii and liis associates liave (Hofmeister's Beitr., lOOfi (8), 121: lOOS 

 (111, 11. 7- it I <li'iiioiistrat('d that the liver can form acetone from many snli- 

 slaiices perfused throujjh it in tiie blood, includinfr not only amino-acids of Die 

 fatt\' acid scries, hut also the aromatic radicals of the jirotciii molecule. 



4-«".T<>ur. P.iol. Cliem., lOlS fl4), .128. 



45 Arch. c\p. i'atli. u. I'harni.. 1S90 (42), 149; Erjrch. inn. Aled.. 1908 (1). 

 374. 



