302 VII. ACIDS, AMIDES, ALDEHYDES AND HYDROCARBONS 



Baker^" demonstrated that both optical isomers of straight-chain a- 

 hydroxy acids from C3 to Cs, and also a-hydroxyisovaleric acid, oj-hydroxy- 

 isocaproic acid, and L-/?-imidazole lactic acid can be oxidized by enzyme 

 preparations from rat liver and rat kicbiey, and from hog kidney. At 

 least two enzyme systems, distinct from the lactic dehydrogenase system 

 and the cyclophorase-racemase system, were separated from washed parti- 

 cle and supernatant preparations of liver and kidney. One of these is 

 specific for oxidation of the L-isomer, and the other is specific for that of 

 the D-isomer of the a-hydroxy acids. 



a. a-Hydroxyisobutyric Acid. When a hydroxyl group is introduced into 

 the a-carbon of isobutyric acid, a marked change in properties obtains. 

 Thus, it was shown by Dziewiatkowski and co-workers^^ that hydroxyiso- 

 butyric or acetonic acid, (CH3)2-C(OH) -COOH), was largely excreted as 

 such without conjugation with glucuronic acid. Moreover, no ketone for- 

 mation occurred. This is in striking contrast to the behavior of isobutyric 

 acid, (CH3)2-CH-COOH, and isobutyl alcohol, which Ringer and asso- 

 ciates^^ found was converted to glucose by the phlorhizinized dog to the ex- 

 tent of three carbon atoms. Acetoacetic acid was also shown to be formed 

 when /3-hydroxyisovaleric acid, (CH2)3: C(OH) -CHsCOOH, was perfused 

 through the surviving liver ;^^ this latter compound has the same grouping 

 ((0113)2 -0(011).) as is present in hydroxy isobutyric acid. 



{2) l3-Hydrox2j and fS-Keto Acids 



The most common acids in this category are ;S-hydroxybutyric acid and 

 acetoacetic (diacetic) acid. The hydroxy and keto acids in this category 

 are interconvertible in the animal body. Thus, Breusch and Tulus^^ 

 found that not only is the a-keto acid, pyruvic acid, reduced by minced 

 tissue, but the same is true of the /3-keto acids, /3-ketobutyric acid and /3- 

 ketocaprylic acid (CH3 • (OH2)4 • 00 • CH2 • OOOH) . It will be recalled that 

 the oxidation of fatty acids regularly proceeds by oxidation of the |S-carbon 

 atom to a keto group. In the case of long-chain acids, a rupture of the 

 acid occurs at the /S-carbon, yielding an acetic acid molecule and an alde- 

 hyde having two less carbons than the original acid. The aldehyde is 

 oxidized to an acid, which again is subject to /S-oxidation, with the forma- 

 tion of a new (8-keto acid which is metabolized similarly. When the fatty 

 acid chain is reduced to four carbons, the sequence of events is interrupted 



30 C. G. Baker, Arch. Biochem. Biophys., 4I, 325-332 (1952). 



3i E. Friedmann, Beitr. chem. Physiol. Pathol, 11, 365 (1908). 



32 F. L. Breusch and T. Tulus, Arch. Biochem., 11, 499-506 (1946). 



