16 CHOLINE 



thenic acid,^ and /S-mercaptoethylamine.^- ^' ^ It is probable that the nucleo- 

 side is joined to the terminal alcoholic hydroxyl of the pantothenate by a 

 pyrophosphate bridge and that the sulfur component forms an acid amide 

 linkage with the carboxyl of the /3-alanine moiety of the pantothenate. 

 The pantothenic acid-mercaptoethylamine complex can be obtained from 

 CoA by hydrolysis by intestinal phosphatase^"- ^^ and is identical with 

 Snell's Lactobacillus hulgaricus growth factor (LBF or pantetheine).^- " 



The free-SH group is the principal site of reactivity in the CoA molecule, 

 and it is readily acetylated to acetyl CoA (CoA — S — CO — CH3) in the 

 presence of ATP. A partially purified preparation of acetyl CoA has been 

 obtained from baker's yeast by Lynen et alP This molecule, formerly 

 designated "active acetate," serves as a donor of acetyl groups in the 

 presence of specific apoenzymes. Energy in the form of ATP is required 

 for its formation, and it is of considerable interest that its acyl-mercaptide 

 linkage is an energy-rich bond.^*"^^ CoA may exist in the disulfide form 

 (CoA — S — S — CoA), and mixed disulfides with other sulfhydryl compounds 

 have complicated its isolation. 



The application of these findings to the metabolism of choline is illus- 

 trated by the system which transfers acetyl from citrate to choline. Ochoa 

 et al}^ have isolated a condensing enzyme from heart muscle which cata- 

 lyzes reversibly the reaction between acetyl CoA and oxalacetate to give 

 CoA and citrate. If choline and a second acetyl-transferring enzyme (acetyl- 

 ase) are present in addition to Ochoa's condensing enzyme plus citrate and 

 CoA, acetylcholine is formed.^^ 



The probable identity of the factor (presumably CoA) required in the 

 acetylation of sulfanilamide and of choline was indicated in 1946.^'' Subse- 

 quently, Nachmansohn obtained a fraction termed acetylkinase from pigeon 

 Uver and demonstrated that both sulfanilamide and choline were acetylated 



■> J. Baddiley and E. M. Thain, /. Chem. Soc. 1951, 3421. 



8 W. H. DeVries, W. M. Govier, J. S. Evans, J. D. Gregory, G. D. Novelli, M. 

 Soodak, and F. Lipmann, J. Am. Chem. Soc. 72, 4838 (1950). 



9 E. E. Snell, G. M. Brown, V. J. Peters, J. A. Craig, E. L. Wittle, J. A. Moore, 

 V. M. McGlohon, and O. D. Bird, J. Am. Chem. Soc. 72, 5349 (1950). 



10 G. D. Novelli, N. O. Kaplan, and F. Lipmann, Federation Proc. 9, 209 (1950). 

 " G. M. Brown, J. A. Craig, and E. E. Snell, Arch. Biochem. 27, 473 (1950). 



12 F. Lynen, E. Reichert, and L. Rueff, Ann. 574, 1 (1951). 



13 F. Lynen, E. Reichert, Angew. Chem. 63, 47 (1951). 



" J. R. Stern, B. Shapiro, E. R. Stadtman, and S. Ochoa, /. Biol. Chem. 193, 703 



(1951). 

 "E. R. Stadtman, J. Biol. Chem. 196, 535 (1952). 



" S. Ochoa, J. R. Stern, and M. C. Schneider, J. Biol. Chem. 193, 691 (1951). 

 " F. Lipmann and N. 0. Kaplan, J. Biol. Chem. 162, 743 (1946). 



