ACETIC ACID AND ACETATE 265 



preted the data as indicating that, in tiiis instance, the animal could utilize 

 the acetylated derivative of the unnatural isomer more readily than that 

 of the natural isomer. On the basis of these results, Ivnoop and Blanco 

 were led to abandon the theory that acetylation is a normal intermediary 

 process in the metabolism of amino acids. 



du Vigneaud and Meyer^^ were able to estabhsh the fact that the acetyl- 

 D-phenylalanine has a specific rotation, [a]D = ~51°, which is identical 

 with that of the compound isolated by luioop and Blanco. It thus 

 appeared that the acetyl derivative was that of the unnatural form of 

 phenylalanine. Subsequently, du Vigneaud and Irish*" proved that the 

 dog can oxidize the natural acetyl-L-phenylalanine more readily than 

 acetyl-D-phenylalanine. Smce this obstacle to the acceptance of the 

 original theory of Knoop was removed, du Vigneaud and Irish^° were in 

 favor of reestablishing the acetyl theory for the in vivo synthesis of an 

 amino acid from the corresponding keto acid. The in vivo conversion of 

 an unnatural to a natural amino acid is believed to occur by formation of 

 the keto acid, followed by formation of the natural acetylated amino 

 acid. The intermediary formation of the keto acid in the in vivo con- 

 version of D-phenylaminobutyric acid to acetyl-L-phenylaminobutyric 

 acid has been proved by the demonstration that practically all of the nitro- 

 gen of the origmal D-acid is replaced by new nitrogen in the L-acetyl 

 compound.*^ Acetic acid, therefore, becomes a most important inter- 

 mediate in amino acid metabolism. 



Lipmann^^ reported that acetate is about twice as effective as acetoace- 

 tate or pyruvate m effecting acetylation of sulfanilamide, when liver homo- 

 genates or extracts are used as the source of the enzyme. The greater 

 effectiveness of acetate over that of the other acetyl precursors is to be 

 expected, smce they must necessarily be converted to acetate before they 

 can be active. In addition to the enzyme, adenyl pyrophosphate is re- 

 quired. 



Acetylation proceeds most effectively under aerobic conditions. Thus, 

 Lipmann*^ found that five times as much acetyl sulfanilamide was formed 

 when air was present, as under anaerobic conditions. Inhibitors of oxida- 

 tion, such as arsenious oxide or iodoacetate, hkewise abohsh acetylation.^^ 

 Although oxygen is not required in the direct acetylation reaction, it is 

 apparently essential to supply the energy needed for condensation. How- 



" V. du Vigneaud and C. E. Meyer, /. Biol. Chem., 98, 295-308 (1932). 

 «» V. du Vigneaud and O. J. Irish, J. Biol. Chem., 122, 349-370 (1937). 

 *' V. du Vigneaud, M. Cohn, G. B. Brown, O. J. Irish, R. Schoenheimer, and D. 

 Rittenberg, J. Biol. Chem., 131, 273-296 (1939). 



" F. Lipmann, /. Biol. Chem., 160, 173-190 (1945). 



