304 VII. ACIDS, AMIDES, ALDEHYDES AND HYDROCARBONS 



(S) Miscellaneous Hydroxy and Keto Acids 



Breusch and Tulus'^- reported that only a- and /?-keto acids can be at- 

 tacked by tissue enzymes. In compounds such as 7-ketovaleric acid 

 (CH3 • CO • CH2 • CH2 • COOH) and 5-ketocaproic acid (CH3 • CO • CH2 • CH2 • - 

 CH2- COOH), in which the ketones were further removed from the carboxyl 

 group, the tissue enzymes were unable to metabolize them. 



Polyketonic acids are readily metabolized in some cases. In fact, ac- 

 cording to the multiple alternate oxidation theory as proposed by Hurtley^^ 

 and later by Jowett and Quastel,^^ and supported by Stadie,^^ polyketonic 

 acids are believed to be formed in the catabolism of fatty acids; such com- 

 pounds can then break down simultaneously at several points to smaller 

 fragments. 



The Q;,7-diketo acids are somewhat difficult to break down. However, 

 the simplest member of this group, acetopyruvic acid (CH3-CO-CH2-CO-- 

 COOH), is apparently rapidly metabolized by animal tissues," and a spe- 

 cific enzyme which produces pyruvic acid from this compound has been 

 partially purified by Meister and Greenstein.^^ On the other hand, 01,7- 

 diketooctanoic acid (CHa-CH.-CHo-CHa-CO-CHa-CO-COOH), is only 

 slowly metabolized by broken cell preparations of liver, in contradistinction 

 to the rapid catabolism of octanoic acid.^^ There is no evidence from 

 the tests of Weinhouse and co-workers^^ with carboxyl-labeled octanoic acid 

 that an a;,7-diketo acid is formed. 



The /3,5-diketo acid has been showTi to be readily metabolized. Thus, 

 Witter and Stotz^° found that rat liver homogenate and an enzyme pre- 

 pared from liver were able to break dowi\ triacetic acid into a molecule of 

 acetate and one of acetoacetate, as indicated below: 



H20 

 CHa-COCHa-COCHa-COOH > CHs-COCHaCOOH + CH3COOH 



Triacetic Acetoaoetic Acetic 



acid acid acid 



The corresponding ethyl ester of triacetic acid was metabolized in a similar 

 manner to the free acid, after the preliminary action of an esterase. Breusch 

 and Ulusoy^^ reported that a 5-lactone of triacetic acid was also metab- 



^* W. H. Hurtley, Quart. J. Med., 9, 301-408 (1915-1916). 



36 M. Jowett and J. H. Quastel, Biochem. J., 29, 2159-2180 (1935). 



36 W. C. Stadie, Physiol. Revs., 25, 395-441 (1945). 



37 A. Lehninger, J. Biol. Chem., I48, 393-404 (1943). 



3« A. Meister and J. P. Greenstein, Federation Proc, 7, 173 (1948). 



33 S. Weinhouse, G. Medes, and N. F. Floyd, J. Biol. Chem., 165, 143-151 (1949). 



« R. F. Witter and E. Stotz, /. Biol. Chem., 176, 501-510 (1948). 



" F. L. Breusch and E. Ulusoy, Arch. Biochem., I4, 183-191 (1947). 



