132 



III. 



OXIDATION AND METABOLISM 



found to be much more ketogenic than the unnatural one.*"^ It was shown 

 almost simultaneously by Baer and Blum^°^ that a greatly increased excre- 

 tion of (S-hydroxybutyric acid followed the administration of 33.7 g. of the 

 amino acid to a diabetic patient. Butts and co-workers^"^ confirmed the 

 fact that leucine gives rise to ketone bodies when fed to normal fasting rats; 

 moreover, no glycogen was formed in rats after the administration of this 

 amino acid. This confirms earlier reports^°'*~^'° that leucine is not a glu- 

 cose-former. Finally, Edson^^^ noted that acetone bodies were formed by 

 liver slices when leucine was added to the substrate. This finding was 

 confirmed by Cohen. ^"^ 



The pathway of metabolism of leucine, as pictured by Lusk,^^^ is given 

 below 



The Conversion of Leucine to j3-Hydroxybutyric Acid^'^ 



A number of reports also indicate that isovaleric acid, one of the inter- 

 mediates postulated in the leucine -^ j8-hydroxy-butyrate reaction, is 

 ketogenic. Thus, Cohen'"^ and Lang and Adickes^^' found that liver 

 slices converted isovaleric acid into ketones. Zabm and Bloch,^^^ employ- 

 ing labeled isovaleric acid, which was incubated with liver slices, showed 

 that the isovaleric acid was broken at the /3-carbon to yield a 2-carbon and a 

 3-carbon fragment. The isopropyl moiety was believed to be the more 

 important source of the ketone bodies. In contradistinction to the 



305 G. Embden, Beitr. chem. Physiol. Pathol., 11, 348-355 (1908). 



™^ J. Baer and L. Blum, Naumjn-Schmiedeberg's Arch, exptl. Pathol. Pharmakol., 55, 

 89-115(1906). 



3«' J. S. Butts, H. Blunden, and M. S. Dunn, J. Biol. Chem., 120, 289-295 (1937). 



3«8 O. Simon, Z. phy.siol. Chem., 35, 315-323 (1902). 



309 R. H. Wilson and H. B. Lewis, /. Biol. Chem., 85, 559-569 (1929-1930). 



"0 J. T. Halsev, Am. J. Phijsiol, 10, 229-235 (1903-1904). 



311 N. L. Edson, Biochem. J., 29, 2498-2505 (1935). 



'I'' G. Lusk, Science of Nutrition, 4th ed., Saunders, Philadelphia, 1928, pp. 235, 640, 

 681. 



313 K. O. St. A. Lang and F. Adickes, Z. physiol. Chem., 263, 227-234 (1940). 



'1* I. Zabin and K. Bloch, J. Biol. Chem., 185, 117-129 (1950). 



