16 II. BIOSYNTHESIS 



these, the acetylphosphate system, can yield acetylphosphate by means 

 of bacterial enzymes. The second mechanism for acetate activation is the 

 ATP-acetate system; the formation of active acetate in mammaUan and 

 in avian tissues requires the mediation of ATP. Apparently acetylphos- 

 phate is not formed in the case of the second type of activated acetate, al- 

 though there may be an intermediary formation of a phosphorylated form 

 of Co A. For a further discussion, see the section on CoA on page 27. 



As regards the synthesis of fat from carbohydrate, Rittenberg and 

 Bloch^^ suggested that the intermediate compound, pyruvate, might not 

 necessarily pass through the stage of acetate, but that it might be directly 

 employed for the synthesis of fatty acids; it was suggested that a pre- 



liminary formation of acylpyruvic acid, CHsC^- COOH, might occur, 



\r 



and that this compound would then be directly decarboxylated . The net 

 result would be the same as if a molecule were directly added, but an ace- 

 tate molecule would not actually be set free. It has also been suggested 

 by Anker^^ that the units used for fatty acid synthesis might not invariably 

 be identical. 



In spite of the uncertainty as to the identity of acetate and the fat 

 precursor from carbohydrate, a number of experiments indicate that this 

 identity exists. For example, French and Popjak^^ proved that, when 

 carboxyl-C^^ acetate, C^^-glucose, or C^^-starch was fed to lactating rabbits, 

 the labeled fatty acids obtained in the milk six hours later were remarkably 

 similar. Moreover, the same amount of radioactive acetyl was incor- 

 porated into p-amino benzoic acid, irrespective of whether the normal 

 rabbit was fed glucose or acetate containing C^**. This also indicates that 

 acetate in an intermediate of glucose, regardless of whether the site of trans- 

 formation is the mammary gland (as in the lactating animal) or extramam- 

 mary tissue (as in the normal rabbit). 



Further evidence for the assumption that acetate is the intermediate in 

 the glucose — >- fat transformation has likewise been recorded by Popjak.^ 

 If the course of synthesis of the fatty acids involves the following changes, 

 as seems probable, Glucose -> Pyruvate — »- Acetate -> Fatty acid, then 

 the incorporation of C^^ should be identical, irrespective of whether this 

 isotope is introduced into the a- or /^-position of pyruvate, or into either 

 the carboxyl or the methyl group of acetate. Popjak^ proved that such is 

 the case; moreover, it was shown, on the one hand, that the position of 



" H. S. Anker, /. Biol. Chem., 176, 1337-1352 (1948). 



"T. H. French and G. Popjdk, Biochem. J., 49, iii-iv (1951). 



