GERARD: NERVE METABOLISM AND FUNCTION 583 



pears to be the only possible first link to a metabolic chain of events. 

 (Electron shifts within single molecules or lattices, if such occur, would 

 themselves follow the shift of charged ions, unless large electromagnetic 

 fields were applied— fields that seem beyond a range of possible bio- 

 logical significance.) However, changed ion concentration is easily 

 sufficient to initiate other local chemical changes. 



Altered metabolism means changes in the rates of chemical reactions. 

 Not only are quantitative increases or decreases of total metabolism the 

 sum of similar variations in the rates of the component reactions; but 

 also qualitative changes are the resultant of increase in rates of certain 

 reactions and decreases in others. The rate of a given reaction is 

 determined by the concentration of active reactants and products and 

 by the catalytic conditions (temperature, water, ions, etc.), especially 

 by the enzyme activity. Reactant concentrations can change only 

 as a result of an antecedent change in another chemical system which 

 produces them — which gets us no further in our problem — or of a 

 spatial redistribution. If reactants are themselves ions, and so moved 

 by the stimulating currents, this could be a direct result of stimulation. 

 In most cases, however, as emphasized by Hober, such a redistribution 

 would also demand prior changes in the system to increase the physical 

 availability, changes in membrane barriers, surface adsorption, and the 

 like. These might also be a direct effect of the stimulus, as the rota- 

 tion of a polar molecule, but are more likely to be secondary to more 

 extensive chemical changes. 



In contrast to the relatively unpromising situation for substrate al- 

 teration, a modification of enzyme activity, and so of metabolism, by 

 ion changes is both theoretically probable and experimentally estab- 

 lished. Besides a direct ion effect on the activity of given enzyme 

 molecules, there exist the other possibilities of activating pro-enzymes 

 (Ca on prothrombin), removing inhibitors (phosphate or citrate bind- 

 ing calcium), and adding accelerators (Cu on thiol oxidation*^). Such 

 ion effects are richly present in biological systems, as well as in the 

 non-living systems mentioned by Dr. Alexander, and it may be useful 

 to itemize some that are important in muscle and nerve tissiies.^^' ^^ 



Magnesium ion either is essential to, or materially hastens, a number 

 of key reactions in carbohydrate degradation, while local increase in its 

 concentration would suffice to initiate or accelerate them. The phos- 

 phorylation of glucose to hexose-6-phosphate by hexokinase, a reaction 

 of especial importance in neural tissue which "prefers" glucose to glyco- 

 gen as a fuel, requires Mg""*; as does, also, the shift of phosphate from 

 the 1 to 6 position by glucophosphomutase.^'* The further phosphory- 



