62 II. DIGESTION AND ABSORPTION OF FATS 



triphosphate (ATP) and choline, according to the following reaction (1). 

 O O 



+ -HOH li + 



CH 3 COH + HOCJH 2 CH 2 N(CH 3 ) 3 > CH 3 COCH 2 CH 2 N(CH 3 ) 3 



Acetic Choline Acetylcholine 



acid 



The Synthesis of Acetylcholine in the Presence of Choline Acetylase (1) 



Feldberg and Mann 361 confirmed the results of Nachmansohn and collabo- 

 rators; they also demonstrated that practically no synthesis of acetyl- 

 choline occurred under aerobic conditions. Reduced glutathione and cys- 

 teine strongly activated the aerobic synthesis of acetylcholine. On the 

 other hand, oxidized compounds were found to inhibit the ester synthesis. 

 Glucose, fructose, and certain phosphohexoses blocked acetylcholine syn- 

 thesis, since the sugars esterified the labile phosphate groups of ATP. 

 Finally, it was reported that K + enhanced the synthetic reaction and Ca ++ 

 inhibited it. Feldberg 362 demonstrated that cell-free powdered dried brain, 

 when suspended in saline solution with eserine and ether, was able to effect 

 a synthesis of acetylcholine at room temperature greater than under any 

 other conditions so far observed. 



According to Lipmann and collaborators, 363,364 pantothenic acid is re- 

 quired as a coenzyme for the synthesis of acetylcholine, in addition to the 

 specified enzyme and ATP. Balfour and Hebb 365 have shown that the syn- 

 thesis of acetylcholine depends upon the action of coenzyme A (CoA). 

 This explains why pantothenic acid acts as a coenzyme, inasmuch as this 

 vitamin is a component of the CoA molecule. For a complete discussion 

 of CoA, the reader is referred to Volume III. In conjunction with CoA, it 

 was shown that the synthesis of acetylcholine could be accelerated by ace- 

 tate as well as by citrate, both of which could act as acetyl-donors to the 

 system. 366 Lipton and Barron 366 had reported several years earlier that 

 citrate was a suitable substrate, as well as a's-aconitate and acetoacetate. 

 These workers recognized that acetylation of choline required the presence 

 of "active" acetate. 



In the light of the newer understanding of the mechanism of action of 



161 W. Feldberg and T. Mann, J. Physiol., 104, 8-20 (1945). 

 382 W. Feldberg, J. Physiol., 103, 367-402 (1945). 



363 F. Lipmann, N. O. Kaplan, G. D. Novelli, L. C. Tuttle, and B. M. Guirard, J. 

 Biol. Chem., 167, 869-870 (1947). 



364 N. O. Kaplan and F. Lipmann, J. Biol. Chem., 17/, 37-44 (1948). 



365 W. E. Balfour and C. Hebb, J. Physiol., 118, 94-106 (1952). 



366 M. A. Lipton and E. S. G. Barron, /. Biol. Chem., 166, 367-380 (1946). 



