INTERMEniARY METABOLISM 



mained entirely olwcure, apart from the findinsr that the cholesterol 

 side chain, as well as the muleus, was derived from acetate. In the 

 case of the fatty acid, a wider variety of degradative procedures are 

 feasible, so that the isotope concentrations at specific positions of the 

 molecule can be ascertained. The acetic acid employed in these 

 experiments contained the carbon isotope only at the carboxyl carbon. 

 If the fatty acids were formed by successive condensation of C2 units, 

 only the odd-numbered carbon atoms would contain C'^. The car- 

 boxyl group obtained by thermal degradation of the fatty acid was 

 indeed about twice as rich in isotope as the total molecule. This 

 finding eliminates, as the principal synthetic reaction, the addition of 

 one C2 unit to either the a- or co-carbon atom of the preformed fatty 

 acid chain. The position of the isotope in the fatty acid chain can 

 be traced further by oxidative cleavage of the "oleic acid" fraction into 

 pelargonic acid, derived from carbon atoms 10 to 18, and azelaic acid 

 from carbon atoms 1 to 9, of the fatty acid. Both moieties contain 

 deuterium and C^^ to about the same extents. It therefore seems 

 probable that the C2 units are used imiformly for the various parts of 

 the fatty acid chain. If the conden.sation mechanism involved were 

 of the acetaldehyde-aldol type, in analogy to the in vitro synthesis of 

 stearic acid carried out by Kuhn et al. (11), a biological reduction of 

 acetic acid to acetaldehyde would be involved, and this is so far without 

 experimental basis. A Claisen condensation with acetic acid or an 

 acetic acid derivative is a more attractive possibility because the 

 simplest reaction of this type, the condensation to acetoacetate, has 

 definitely been shown to occur. The /3-keto acids which would have 

 to be postulated as intermediates, should contain readily enolizable 

 hydrogen at the alpha position. The fact that deuterium is lost in the 

 conversion of acetate to fatty acid is in accord with the postulated 

 scheme, which may be viewed as a reversal of the steps responsible for 

 fatty acid degradation. The fact that acetic acid is involved in the 

 synthesis as well as in the breakdown of fatty acids, and the revers- 

 ibility of two partial steps, viz., the acetate-acetoacetate reaction and 

 the palmitic acid-stearic acid conversion, are in favor of this scheme. 

 The hypothesis is not out of line with general biochemical experience, 

 if one considers the reversibility of individual reactions in the metabo- 

 lism of proteins and carbohydrates. 



The role of acetic acid as a building unit for fat suggests that 



