GERARD: NERVE METABOLISM AND FUNCTION 589 



tion at the rate of 10~^ mM/gra./hr., would liberate 2 X 10~^ cal./gm./hr. 

 For frog nerve, at 50 impulses per second (and at this frequency the 

 energy per impulse is fully 80% of that at zero frequency) , von Muralt's 

 value gives 10"' mM ACh or 0.02 cal. (If ChE were working at full 

 capacity, the heat liberated just from ACh splitting would be 6 cal. 

 for the ganglion, 0.1 cal. for frog nerve!) But the measured total heat 

 production of frog nerve is, in these units, 0.1 cal. at rest and 0.18 at 

 maximal activity; for mammalian cortex (using the highest values of 

 Q02 reported"") , the resting energy release is 25 cal. and that of maxi- 

 mum activity perhaps 50 cal. These brain values are probably much too 

 high for the ganglion (probably three-fold"^''), but this gives every ad- 

 vantage to ACh. The actual ACh released in nerve during activity 

 would thus, duj-ing its normal hydrolysis by ChE, account for over 10% 

 of the total heat of nerve activity. Yet, only 3% of this heat is initial 

 heat, immediately related to the events of conduction. Moreover, 

 other exothermic reactions are surely involved, even with ACh itself — 

 in its formation, liberation, neutralization, etc. — before that of its 

 destruction. (And again, if ChE were fully active, the ACh hydrolysis 

 heat alone would account for more than the full extra heat production 

 of active nerve!) 



An examination, further, of actual chemical reactions involved in the 

 synthesis of ACh raises added difficulties. The initial energy'- source 

 for ACh synthesis is considered to be CrP. During maximal frog 

 nerve activity, less than 13 mgm. % of CrP is split in an hour; enough 

 to account, at best, for 0.007 cal.^", far below the needs for ACh. But, 

 of course, CrP is resynthesized by energy from other metabolic reac- 

 tions, so this does not mean too much. The total fuel turnover, how- 

 ever, does set an inescapable limit. For bullfrog nerve, 6 mgm. % of 

 carbohydrate disappears per gram per hour at rest or activity ;''® for 

 the small frog nerve, this might be 10 mgm. %, or 6 X 10~^ mM/gm./hr. 

 On complete oxidation, this could yield a maximum of 0.02 mM of CrP, 

 if all the energy available to form high-energ\' phosphate bands (3 per 

 atom of oxygen) were so directed. Thus, the total nerve metabolism 

 could just comfortably synthesize ACh at the rate it is reported actually 

 to form during activity (.01 mM ACh from .02 CrP), and could not 

 begin to supply energy to synthesize it at the rate ChE can destroy it. 

 (Actually, the picture is worse than here presented, because the maxi- 

 mum heat of activity is 0.18 cal./gm./hr. for frog nerve, whereas the 

 assumed carbohydrate oxidation would yield 0.4.) 



It may also deserve thought that, while the esterase is located in the 

 membrane of the giant nerve fiber, the oxidizing enzyme systems are 



