124 E. S. GUZMAN BARRON 



a number of investigators, although no single enzyme has yet been 

 isolated. The classical concept of Knoop (43) and Dakin (25) with 

 the modifications suggested by MacKay (57) — oxidation at their /SC 

 atoms with subsequent removal of two C units which may condense 

 to acetoacetate or to citrate — seems now generally accepted. As in the 

 complete oxidation of carbohydrate, the series of oxidations which 

 take place during the breakdown of fatty acids require the presence of 

 ATP or of C4 dicarboxylic acids, which in their oxidation provide 

 energy-rich phosphate bonds (50, 64, 38). Whether there is a trans- 

 phosphorylation process with the formation of unstable acyl phosphates 

 is not known, in spite of some efforts to prove that such substances are 

 formed. The acyl phosphates (monopalmityl phosphoric acid and mono- 

 octanoylphosphoric acid) , although hydrolyzed much more slowly than 

 acetyl phosphate (51), were physiologically inactive. When octanoic 

 acid was oxidized by the liver in the absence of C* dicarboxylic acids, 

 acetoacetate was the end product (52, 85). In the presence of C4 dicar- 

 boxylic acid, the C2 fragments gave citric acid and its oxidation products, 

 a-ketoglutaric acid, and succinic acid. The interconversion of acetic 

 acid to acetoacetic acid has been demonstrated by direct interconversion 

 (49, 86) as well as by the synthesis of citric acid from acetoacetate pre- 

 sumably by its previous breakdown to "active" acetate (87). This acetic 

 acid, the end product of carbohydrate oxidation and of fat oxidation, is 

 the connecting link of carbohydrate and fat metabolism. The further 

 oxidation of acetic acid, we have already shown (see chart), occurs 

 through the tricarboxylic acid cycle. The synthesis of fat starts with 

 the condensation of acetate to acetoacetate. Indeed, Rittenberg and 

 Bloch (75) demonstrated with isotope experiments that acetic acid is 

 utilized for the synthesis of fats. 



The Oxidation and Synthesis of Proteins 



Proteins in the oxidation of their fundamental units, the amino acids, 

 contribute greatly to the formation of the carboxylic acids which by 

 their reversible coupled oxidation-reductions form the common pathway 

 for the final steps of complete oxidation of foodstuffs, whether it be 

 carbohydrate, fat or protein. The rapid and continuous breakdown and 

 synthesis of proteins so well demonstrated by Whipple and his co- 

 workers (56) and by Schoenheimer and his coworkers (77), as well 

 as the great specificity of proteinases and peptidases, brought forth the 

 suggestion that protein synthesis could be performed by coupled reac- 

 tions between the hydrolytic enzymes. Bergmann and Fruton (16), in 



