122 III. OXIDATION AND METABOLISM 



Neither acetone nor acetoacetic acid contains an asymmetric carbon 

 atom; however, jS-hydroxybutyrate does contain a carbon atom which 

 renders it optically active. Had it not been for the latter fact, the isola- 

 tion of this third ketone body might have been delayed later than 1884, the 

 year in which Kiilz^^^ discovered it. Since a marked levorotation of the 

 urine was noted after the fermentation of the sugar, it was certain that some 

 other abnormal substance, in addition to glucose, was present in the urine. 

 Kiilz succeeded in isolating and characterizing /S-hydroxybutyrate (pseudo- 

 oxybutyric acid). Simultaneously with the work of Kiilz, Stadelmann'^^^ 

 reported the presence of an acid in the urine of diabetics which was incor- 

 rectly described as crotonic acid. Minkowski,^^^ continuing the investiga- 

 tions of Stadelmann, came to the conclusion that the acid in question was 

 not crotonic acid but rather j8-hydroxybutyric acid. 



(b) The Relationship of Ketonuria to the Fatty Acid: Glucose Ratio. The 

 first recognition that ketonuria occurred when insufficient carbohydrate was 

 being oxidized was that of Hirschfeld^^^ in 1895. However, Stadelmann-^^ 

 had pointed out several years earlier that a relationship existed between the 

 formation of j8-hydroxybutyric acid and the occurrence of coma. Magnus- 

 Lgyy265 showed that, when an 11.7 g. dose of /3-hydroxybutyric acid was 

 given to a normal dog, it was completely oxidized and did not appear in the 

 urine; on the other hand, when the acid was administered to a phlorhi- 

 zinized dog, it was largely excreted in the urine. Neubauer"^ found that, 

 when either acetoacetic acid or /3-hydroxybutyric acid was given to a dia- 

 betic patient, both compounds were excreted in the urine. This indicated 

 that the two acids were in equilibrium; in cases of marked ketosis, the /3- 

 hydroxybutyrate comprised 60 to 80% of the total ketone bodies. 



Shaffer^" was the first to suggest a quantitative relationship between the 

 amounts of sugar, protein, and fat metabolized and the quantity of ketone 

 bodies produced. The amomit of ketogenic matter metabolized, calculated 

 in millimoles, was determined by the use of the following constants : 



2'i E. Kiilz, Z. Biol, 20, n.s. 2, 165-178 (1884). 



^''^ E. Stadelmann, Naunyn-Sckmiedeberg's Arch, exptl. Pathol. Pharmakol., 17, 419-444 

 (1883). 



''" O. Minkowski, Naunyn-Schmiedeherg's Arch, cxptl. Pathol. Pharmakol, 18, 35-48 

 (1884). 



2'^ F. Hirschfeld, Z. klin. Med., 28, 176-209 (1895). 



^^ E. Stadelmann, Uher den Einfluss der Alkalien auf den menschlichen Stoffwechsel. 

 Experimentelle-klinische Untersuchungen, Stuttgart, 1890; cited hy G.ljusk, Elements of 

 the Science of Nutrition, 4th ed., Saunders, Philadelphia, 1928, p. 658. 



276 O. Neubauer, Verhandl dent. Kongr. inn. Med., 27, 566-574 (1910). 



2" P. A. Shaffer, J. Biol Chem., 47, 449-473 (1921); 49, 143-162 (1921); 54, 399-441 

 (1922). 



