122 LIFE: ITS NATURE AND ORIGIN 



a prerequisite for any theory correlating chemical reactions with con- 

 duction. Significant amounts of the ester can be metabolized in a 

 millisecond or a fraction thereof. One square millimeter of neuronal 

 surface of the giant axon of Squid, e.g., can split one billion molecules 

 of acetylcholine in one millisecond. The turnover number of the 

 purified enzyme seems to be close to 20 million per minute, which 

 means that one molecule of enzyme can split one molecule of substrate 

 in a few millionths of a second. The enzyme is localized exclusively 

 in the suface where the bioelectrical phenomena occur. It is present 

 in all conducting mechanisms throughout the whole animal kingdom, 

 being found in the lowest animal form possessing neuromuscular tissue 

 (Tubularia, a hydrozoan coelenterate). The enzyme is distinctly 

 different from all esterases present in non-conductive tissues like liver, 

 kidney, pancreas, etc. 53 



"The activity of this enzyme can be correlated in different ways 

 with the electrical manifestations of nerve activity. A close parallelism 

 between voltage and cholinesterase activity has been established in 

 studies on electric tissue. The powerful discharge in these organs is 

 basically identical with the electric potentials produced in nerve and 

 muscle, the only distinction being the arrangement of the units in 

 series. Great variations of the voltage per centimeter are found in the 

 electric organ of Electro phorus electricus, the South American electric 

 eel, whether the organ of a single specimen or that of specimens of 

 different sizes are used. In experiments in which the voltage ranging 

 from 0.5 to 22 per centimeter was plotted against cholinesterase 

 activity, a direct proportionality was found between the physical and 

 the chemical event, the line correlating the two processes passing 

 through zero. These findings indicate the interdependence of the two 

 events. No other chemical reaction offers a comparable behavior. 54 



"Another line of observation was based on thermodynamic con- 

 siderations. If the primary alterations of the surface membrane are 

 connected with the release and removal of acetylcholine, then the 

 primary source of energy during recovery should be used for the resyn- 

 thesis of the ester. In experiments on the electric fish, it can be 

 demonstrated that energy-rich phosphate bonds are adequate to 

 account for the electric energy released during the discharge. If the 

 breakdown of adenosine triphosphate, as suggested in these experi- 

 ments, is the primary energy source in recovery, adenosine triphosphate 

 should yield the energy for acetylation of choline. In agreement with 

 this assumption, a new enzyme, choline acetylase, can be extracted 

 from brain, which in cell-free solution under strictly anaerobic con- 

 ditions, forms acetylcholine in the presence of adenosine triphos- 

 phate. 55 " 58 



"A third line of investigation in which the interdependence of 



