ACIDOSIS AND ACETONURIA 563 



They might readily be formed from proiciiiN through splitting out of the NHj 

 group from the amino-acids; indeed the amino-acids arc generally considered as a 

 source of the acetone bodies/" particularly because, whenever there is considerable 

 pathological breaking-down of proteins, these bodies, especially acetone, may 

 appear in the urine; c. 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, plienylalaninc and tyrosine yield diacetic acid 

 when perfused through the liver, while most of the other amino-acids are able to 

 yield sugar in diabetic animals, 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 destruction that occurs (Magnus- 

 Lev}0>*^ and in diabetes it is often observed that feeding of fats and fatty acids 

 increases the output of acetone bodies, and hence it is evident that acetone bodies 

 may be derived from the fats. /3-oxybiitj'ric acid can be produced readily from 

 fatty acids, especially, of course, from butyric acid, and we usually observe an in- 

 crease in the acetone excretion in a diabetic given large quantities of butter. Other 

 higher fatty acids are also found to cause increased acetone excretion. 



The studies of Knoop,^' and his associates have indicated that in the cata- 

 bolism of fatty acids, the chains are broken down by oxidation of the carbon atom 

 third from the end, that is, the /3-position, and the two end carbon atoms are then 

 split off. Therefore, two carbon atoms are always split off at a time, and hence 

 there can be oxidized into oxybutyric acid only those fatty acids which contain 

 an even number of carbon atoms, which includes the ordinary fatty acids (oleic, 

 palmitic and stearic) of fat tissue, which have each an even number of carbon 

 atoms (16 or 18), and also butyric, caproic and similar acids. Normal fatty acids 

 which contain an odd number of carbon atoms cannot yield oxybutyric acid. 

 However, according to A. Loeb,*^ aceto-acetic acid may be built up from acetic 

 acid in the liver, and the urine in diabetes may contain acetic acid. "The forma- 

 tion of oxj-butyric acid and of diacetic acid in all these cases may be said to be due 

 to the fact that the diabetic organism is not able quite to finish the attack on the 

 beta-carbon atom of butj-ric acid" (Folin). 



From the results of these studies it seems that the acetone bodies can, theoreti- 

 cally be formed from any of the three classes of food-stuffs, but that ordinarily 

 they come chiefly from the fats, and in severe diabetes also to a considerable extent 

 from fatty acids formed by deaminization of amino-acids. Although it is prob- 

 able that the acetone bodies are formed in many if not all tissues, yet there is 

 abundant evidence that the liver plays an important part in ketogenesis, as shown 

 by the decrease in acetone bodies in Eck fistula dogs, and their great increase when 

 the blood supply of the liver is augmented.** 



ACIDOSIS AND ACETONURIA IN CONDITIONS OTHER THAN 



DIABETES"" 



When our chief method of recognition of acidosis consisted of 

 determining the presence of acetone bodies in the urine, the term 

 acetonuria was used as synonymous with acidosis, but we now know 

 that we may have varying degrees of acetonuria without significant 



*" Embden and his associates have (Hofmeister's Beitr., 1906 (8), 121; 1908 

 (11), H. 7-9) demonstrated that the liver can form acetone from many substances 

 perfused through it in the blood, including not only amino-acids of the fatty 

 acid series, but also the aromatic radicals of the protein molecule. 



81 Jour. Biol. Chem., 1913 (14), 328. 



82 Arch. exp. Path. u. Pharm., 1899 (42), 149; Ergeb. inn. Med., 1908 (1), 

 374. 



83 Full bibliography and discussion by Porges, Ergebnisse Physiol., 1910 (10), 

 6. See also Ringer, Jour. Biol. Chem., 1913, Vol. 14. 



8< Biochem. Zeit., 1912 (47), 118. 



85 Fischer and Kossow. Deut. Arch. klin. Med., 1913 (101), 479. 

 85<» See Sellards "Principles of Acidosis, Harvard Press, 1917; also Frothingham, 

 Arch. Int. Med., 1916 (18), 717. 



