14 II. BIOSYNTHESIS 



these activations are achieved in organic compounds by esterification or 

 by anhydride formation; in the case of acetate, it might involve such 

 compounds as acetyl chloride (CHs-CO-Cl), acetic anhydride ((CH3-CO)2- 

 0), ketene (CH2:C0), ethyl acetate (CHs- CO -002115), or acetyl phosphate 

 (CH3-CO-H2P04). 



(a) Acetylphosphate as the Possible Precursor. The formation of ace- 

 tylphosphate along with formate by the phosphoroclastic splitting of pyru- 

 vate is an example of acetylation in the absence of free acetic acid; 

 this occurs in certain bacterial systems. ^"'^^ As recently as 1946, Lipmann^^ 

 had the impression that acetylphosphate might be the active form of 

 acetate. However, Lipmann^^-^^ later showed that acetylphosphate was 

 ineffective in the acetylation of aromatic amines; this reaction was ef- 

 fectively catalyzed by pigeon liver preparations. 



Lynen showed that acetylphosphate^* was unable to combine with oxalo- 

 acetic acid; it was also found that no citrate was formed. ^^ Martins and 

 Lynen^^ presented strong evidence that acetate is oxidized through the 

 citric acid cycle, but that it must be "activated" before it can enter this 

 cycle. ^®'" Another reaction in which acetyl groups participate without 

 the formation of the acetate molecule is afforded in the intermolecular trans- 

 fer of acetyl groups from an N-acetyl amino acid to a free amino acid, 

 as demonstrated in the intact animal. ^^ However, this latter reaction is 

 not one which has such general application as to be considered in the 

 synthesis of fatty acids. 



(h) Coenzyme A a7id ^'Active Acetate.'" The discovery that a coenzyme 

 was involved in effecting the incorporation of the acetate molecule into 

 new compounds was based upon a number of investigations. The interest 

 was intensified in this field when it was realized that "active acetate" was 

 involved not only in the synthesis of citric acid and the acetylation of 

 sulfonamide and of choline, but also in the synthesis of acetoacetate, fatty 

 acids, and the steroid nucleus. The early understanding of these relation- 

 ships should be credited to Schoenheimer, as reported in the E. K. Dun- 



30 F. Lipmann, /. Biol. Chem., 134, 463-464 (1940). 



31 M. F. Utter, F. Lipmann, and C. H. Werkman, /. Biol. Chem., 158,521-531 (1945). 

 " F. Lipmann, Advances in EnzymoL, 6, 231-267 (1948); Harvey Lectures, 44, 99-123 



(1948). 



33 F. Lipmann, Bacteriol. Revs., 17, 1-16 (1953). 



34 F. Lynen, Ber., 73, 367-375 (1940). 



3* N. Neciullah, Thesis, Munich, 1941; cited by F. Lynen, Harvey Lectures, 48, 210- 

 244 (1952-1953), p. 212. 



3« C. Martins and F. Lynen, Advances in Enzymol, 10, 167-222 (1950). 



3' F. Lynen, Ann., 552, 270-306 (1942). 



38 K. Bloch and D. Rittenberg, Federation Proc, 5, 122-123 (1946). 



