HYDROXY AND KETO ACIDS 303 



in the absence of carbohydrate. Under such circumstances, a considerable 

 portion of the keto acid is reduced to the hydroxy acid, and the mixture of 

 tiiese two acids is excreted m the urine. 



Fiu'ther confirmation of the ease of oxidation of the /3-hydroxy and /?- 

 keto acids can be obtained from the classical studies of Grafflin and Green. ^^ 

 These investigators reported that a large number of /3-hydroxy and jS-keto 

 acids, as well as a,jS-unsaturated fatty acids, which have been considered 

 as intermediates m fatty acid catabolism according to the /3-oxidation 

 theory, were as readily oxidized by the kidney cyclophorase system as were 

 the corresponding fatty acids, and that, furthermore, their end-products 

 were also identical with those of the parent acids. When the oxidation of 

 the fatty acid involved the cleavage of a single C2 group, and particularly 

 when one of the products of oxidation was inhibitory, as, for example, pro- 

 pionic acid from valeric acid, oxidation occurred satisfactorily Avhen in- 

 creased amomits of the "sparker" were present. The hydroxy-acids tested 

 included the following DL-acids: /3-hydroxy but\Tic; j8-hydroxyvaleric, 

 CH,-CH.rCH0H-CH2-C00H; /3-hydroxVisocaproic, (CHj^orCH-- 

 CHOHCHoCOOH; /3-hydroxycaproic, CH3CH2CH2CHOHCH.2- 

 COOH ; and /3-hydroxycaprylic ; CH3 • (CH2)4 • CHOH • CH2 ■ COOH. All 

 these acids were readily oxidized. On the other hand, /3-hydrox\dauric 

 acid (CHs- (CH2)8- CHOH -CHa- COOH) was found to be a powerful in- 

 hibitor of fatty acid oxidase, even at concentrations of less than 0.1 micro- 

 mole per ml. Here again, 75% of this acid was oxidized when highl}" potent 

 enzyme preparations were employed. 



The /3-keto acids tested by Grafflin and Green" were likewise readilj^ 

 oxidized. The samples tested were the following: /3-ketovaleric acid, 

 CH3CH2COCH2COOH; ^-ketoisocaproic acid, (CH3)2:CH-CO-CH2-- 

 COOH; and /3-ketooctanoic acid, CH3-(CH2)4-CO-CH2-COOH. The 

 several intermediates of fatty acid oxidation were similarly broken down 

 i)y a li^•er cyclophorase. Similar results were obtained by Witter et al.^^ 

 with their washed li^'er homogenates which were able to metabolize (3-hy- 

 droxyhexanoate, |3-ketohexanoate, and, to some extent, /3-h3'droxy-7- 

 hexenoate (CH3 • CH : CH • CHOH -CHs- COOH), but not a,^-dihydroxy- 

 hexanoate (CH3-CH2-CH2- CHOH -CHOH -COOH) or triacetic acid 

 (CH3 • CO • CH2 • CO • CHo • COOH) . 



These experiments are all consistent in demonstrating that the /3-hydroxy 

 and /?-keto acids are readily metabolized products which follow the same 

 course of metabolism as do their parent acids. 



" R. F. Witter, E. H. Xewcomb, and E. Stotz, J. Biol. Chem., 185, 537-548 (1950). 



