IV. BIOCHEMICAL SYSTEMS 17 



in the presence of the enzyme, ATP, and acetate. ^^ It may be assumed that 

 the fraction contained CoA as well as acetylkinase. Choline acetylase was 

 inhibited or inactivated by iodoacetate.^^ Thiolacetate would replace the 

 ATP and acetate in this system and in acetylating systems prepared from 

 brain and from Escherichia coli extracts, but not in the system obtained 

 from ganglia from the head of the squid.^" Surprisingly, dimethylamino- 

 ethanol was esterified at the same rate as was choline whereas neither 

 aminoethanol nor monomethylaminoethanol was active. It is of interest 

 that the acetic acid ester of dimethylaminoethanol bears no resemblance 

 in biological activity to the corresponding trimethyl compound, acetyl- 

 choline. Although revisions may be necessary in the present understanding 

 of phosphorylations during the acetylation of choline, it is reasonable to 

 assume that a failure to find changes in concentrations of either inorganic 

 phosphate or in ATP-^ may be ascribed to the presence of acetyl CoA or, 

 possibly, of a substance such as thiolacetate. 



The recognition of the indispensable role of a derivative of pantothenic 

 acid in the metabolism of acetate involves this vitamin in the over-all 

 synthesis of fatty acids from carbohydrate and, hence, in the production of 

 fatty livers. The same possibility is recognized in the case of thiamine 

 because of the role of diphosphothiamine in pyruvate metabolism.- ■ -^ The 

 role of the vitamins of the B complex in choline-deficient animals is dis- 

 cussed in Section IV, p. 33. 



The extreme physiological activity of acetylcholine makes it understand- 

 able that rapid inactivation is essential as part of the mechanism controlling 

 its concentration in tissues. Acetylcholine is hydrolyzed at various rates 

 by miscellaneous tissue esterases and at a rapid rate by pseudocholinester- 

 ase and by cholinesterase. An attempt at differentiation on the basis of 

 substrate specificity has been made-^ and reports have appeared on the 

 localization in tissues-^ and on inhibitors-^- -^ of a specific acetylcholinester- 

 ase. A more satisfactory definition of a specific acetylcholinesterase and its 

 description must await the isolation and characterization of such an en- 

 zyme. 



'^ D. Nachmansohn, J. B. Wilson, S. R. Korey, and R. Berman, J. Biol. Chem. 195, 



25 (1952). 

 1^ D. Nachmansohn and A. L. Machado, J. Neurophysiol. 6, 397 (1943). 

 2» S. R. Korey, B. de Braganza, and D. Nachmansohn, /. Biol. Chem. 189, 705 (1951). 

 21 N.-V. Thoai, L. Chevillard, and S. Mayer, Compt. rend. 229, 254 (1949). 

 " R. A. Peters and J. R. O'Brien, Ann. Rev. Biochem. 7, 305 (1938). 

 " E. S. G. Barron, C. M. Lyman, M. A. Lipton, and J. M. Goldinger, /. Biol. Chem. 



141, 957 (1941). 

 '^'^ K. Augustinsson and D. Nachmansohn, Science 110, 98 (1949). 

 " G. B. Koelle, J. Pharmacol. Exptl. Therap. 103, 153 (1951). 

 2« M. G. Ord and R. H. S. Thompson, Biochem. J. 46, 346 (1950). 

 " W. N. Aldridge, Biochem. J. 46, 451 (1950). 



