VOL. 12 (1953) BIOCHIMICA ET BIOPHYSICA ACTA 315 



CHOLINE ACETYLASE SPECIFICITY IN RELATION 

 TO BIOLOGICAL FUNCTION* 



by 



RUTH BERMAN. IRWIN B. WILSON and DAVID NACHMANSOHN 



Department of Neurology, College of Physicians and Surgeons, 

 Columbia University, New York, N.Y. [U.S.A.) 



INTRODUCTION 



Otto Warburg's achievements have greatly influenced contemporary biology and 

 biochemistry in many respects. One of the outstanding features of his work has been his 

 early emphasis on energy -yielding chemical reactions in cells as a key for a better under- 

 standing of cellular function. It was this particular aspect which impressed Otto 

 Meyerhof and - under the influence of Otto Warburg - attracted him to cellular 

 physiology. The work of these two leaders on the energy transformations in cellular sj^s- 

 tems have revolutionized the thinking of our generation of biochemists. 



From the studies of intermediate carbohydrate metabolism emerged the recognition 

 that the paramount role of the glycolytic cycle is the generation ot ATP. The energy of 

 hydrolysis of this nucleotide is generally assumed to be used m the elementary process 

 of muscular contraction. In studies aimed at the analysis of the elementary process of 

 nerve impulse conduction and the sequence of energy transformations associated with 

 this function, evidence has been obtained that the release of acetylcholine and its action 

 upon a structural protein is the primary chemical reaction responsible for the generation 

 of the bioelectric currents, which propagate the nerve impulse^'^. The action of acetyl- 

 cholinesterase is the rapid hydrolysis of the ester enabling the nerve to return to its 

 resting state. Since it was found, in experiments on electric fish, that the energy re- 

 leased by the breakdown of phosphorylated compounds is adequate to account for the 

 total energy released during activity, it was postulated that the energy of ATP in hydrol- 

 ysis is used for the resynthesis of the acetylcholine split in the primary process, in other 

 words, provides 'the energy for acetylation. This postulate was borne out by experiment. 

 It was shown, in 1943, that cell-free extracts of brain and electric tissue may acetylate 

 choline in presence of ATP^. These experiments were the first demonstration that ATP 

 provides energy for synthetic reactions outside the glycolytic cycle in addition to its 

 role in muscular contraction. It initiated intensive studies in many laboratories on the 

 mechanism of acetylation generally. 



* This work was supported (in part) by the Medical Research and Development Board, Of&ce of the 

 Surgeon General, Department of the Army, Contract No. DA-49-007, and in part by the Division of 

 Research Grants and Fellowships of the National Institutes of Health, H-740, United States Public 

 Health Service. 



References p. 324. 



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