HYDROXY AND KETO ACIDS 301 



2. Hydroxy and Keto Acids 



Important intermediates in the catabolism of the fatty acids, as well as 

 in the degradation of glucose and amino acids, include hydi-oxy and keto 

 acids. 



{1) a-Hydroxy and a-Keto Acids 



There are several common a-hj^droxy acids in the animal body. One 

 of these is lactic acid (CHs-CHOH-COOH), which originates from carbo- 

 hydrate, as w^ell as from the hydrolytic deamination of alanine. More 

 complex a-hydroxy fatty acids include cerebronic acid (CH3-(CH2)2i-- 

 CHOH.COOH) and hydroxynervonic acid (CH3.(CH2)7.CH:CH.(CH2)i2- 

 CHOH • COOH) , both of which are important components of cerebrosides. 



Keto acids may be formed by controlled oxidation of the corresponding 

 hydroxy acids. Lactic acid is readily converted to pyruvic acid, while the 

 reverse change is also known to occur. The prime importance of a-keto 

 acids in the metabolic picture is realized when one recalls that pyruvic acid, 

 and several members of the tricarboxylic acid cycle, such as a-ketoglutaric 

 and oxaloacetic, are a-keto acids. 



Most of the naturally occurring amino acids are a-amino acids. Since 

 it is know that the first step in their catabolism is deamination, it is obvious 

 that hydroxy and keto acids can be formed from them. Thus, w^hen hy- 

 drolytic deamination occurs, a-hydroxy acids are formed and, when oxida- 

 tive deamination obtains, the a-keto acids result. 



The commonest method for the oxidation of a-hydroxy acids involves {1) 

 conversion to an a-keto acid, {2) decarboxylation with the formation of an 

 aldehyde having one less carbon than the original acid, {3) oxidation of 

 aldehyde to acid, and (4) oxidation of the resulting acid by /3-oxidation. 



Both hydroxy and keto acids may likewise be converted to the corre- 

 sponding amino acids by amination. As proof of these syntheses, one may 

 cite the fact that the essential acids, tryptophane, valine, and histidine, 

 may be replaced in the diet by corresponding a-hydroxy acids. More- 

 over, the a-keto acids, as well as the a-hydroxy acids, have been shown to 

 replace phenylalanine, leucine, and isoleucine. 



Since the hydroxy acids contain an asymmetric carbon, they are optically 

 active. Although it is recognized that only one of the optical isomers oc- 

 curs naturally, the appropriate form can usually be synthesized by the 

 body. The abihty of a-keto acids to serve as a source of the amino acids 

 which likewise contain an asymmetric a-carbon is evidence for this in vivo 

 capacity. 



