ENZYMES CONCERNED WITH DIGESTION OF LIPIDS 61 



ions caused an increase in the free form at the expense of the combined 

 form. 356 Synthesis of acetylcholine was inhibited by NH 4 + . 



Elliott and Henderson 354 found that a low concentration of free acetyl- 

 choline may be maintained in brain in the absence of an anticholinesterase 

 (inhibitor). Bound acetylcholine in brain slices is considerably increased 

 when the tissues are incubated anaerobically in the presence of glucose, 

 whether or not anticholinesterase is present. The increase is less marked in 

 the presence of a high potassium ion concentration, especially when anti- 

 cholinesterase is absent. It is suggested that the release of acetylcholine 

 from the bound form is reversible. 



The acetylcholine content of rat brain was shown to vary with the in- 

 tensity of activity. Thus, Richter and Crossland 357 found that the level 

 during anesthesia is 300% above that during convulsions. Elliott et al. 35S 

 also noted that the administration of nembutal to the cat, as well as to the 

 rat, caused brain acetylcholine to increase greatly. The level of acetyl- 

 choline decreases as the anesthesia wears off, but it can be raised again by a 

 new administration of the drug. 358 Other anesthetics such as metrazol 

 or picrotoxin increase acetylcholine to some extent in unnarcotized cats, 

 although the administration of these anesthetics decreases the brain acetyl- 

 choline level in cats given nembutal. 358 Richter and Crossland 357 observed 

 that the fall in acetylcholine which follows electrical stimulation is transi- 

 ent, and is rapidly reversed on the cessation of the stimulation. The rate 

 of resynthesis of acetylcholine under these conditions was found to be 7 fxg. 

 per gram of brain per minute. 



d. Choline Acetylase. (a) Introduction. Although it is generally as- 

 sumed that the same enzymes catalyze both the synthetic and the hydro- 

 lytic reaction, the enzymes responsible for the synthesis and degradation of 

 acetylcholine have generally been considered to be separate entities. While 

 those which effect hydrolysis of this compound are called cholinesterases, 

 those which promote the synthesis of choline and acetic acid to the ester 

 are referred to as choline acetylase. Choline acetylase can be separated 

 from cholinesterase by means of acetone; this solvent completely inacti- 

 vates the cholinesterase. 359 



(6) Mechanism of Action. Nachmansohn and John 359 and Nachmansohn 

 and Machado 360 were the first to demonstrate that the homogenized brain 

 tissue synthesizes acetylcholine anaerobically in the presence of adenosine 



356 P. J. G. Mann, M. Tennenbaum, and J. H. Quastel, Biochem. J., 33, 822-835 (1938). 



357 D. Richter and L. Crossland, Am. J. Physiol., 159, 247-255 (1949). 



388 K. A. Elliott, R. L. Swank, and N. Henderson, Am. J. Physiol., 162, 469-474 (1950). 

 369 D. Nachmansohn and H. M. John, /. Biol. Chem., 158, 157-171 (1945). 

 360 D. Nachmansohn and A. L. Machado, ./. Neurophysiol., 6, 397-403 (1943). 



