584 ANNALS NEW YORK ACADEMY OF SCIENCES 



lation of this substance, an intermediate in the glycogen as well as 

 glucose reaction chain, to fructose 1,6-diphosphate, also requires Mg^*. 

 The later change in phosphoglyceric acid to the energy-rich phos- 

 phoenol-pyruvic acid involves a magnesium combination with enolase, 

 and fluoride inhibition of this reaction depends on displacement of 

 Mg^* by a fluoride complex. ^^ Magnesium or manganese, as well as 

 calcium (K inhibits), is an essential component of the system which 

 forms ATP and pyruvic acid from the phosphopyruvic acid and a lower 

 adenosin phosphate.*" This ion is again reported necessary for the 

 splitting of ATP to ADP by myosin,^' although most workers*^' *''• ^° 

 find Mg"""^ inhibitory here. Mg*"" also inhibits the shift from 3-phos- 

 phoglyceric acid to 2-phosphoglyceric acid by phosphotriose mutase.^^ 



Calcium ion, as mentioned, is required for the formation of ATP 

 from phosphopyruvic acid. It is also involved in splitting a phosphate 

 from ATP by myosin or other ATP-ases'*^' ^'^' -'^ and, perhaps, in the 

 accompanying shortening of the myosin fibers. The splitting of acetyl- 

 phosphate to acetate and phosphate is accelerated by Ca"^"^.^* And, 

 again, to mention an inhibitory action, Ca""* interferes with the forma- 

 tion of acetylcholine from choline. ^^ 



The formation of ATP is thus influenced by all three of the major 

 cellular cations (Mg, Ca, K) ; its destruction, by at least two (Mg, Ca). 

 ATP, in turn, is critical in both fat and carbohvdrate oxidation and 

 may be one of the regulators of metabolism. Thus, a lowered ATP 

 concentration might favor utilization of carbohydrate over fat'^*' and 

 glycolysis over respiration.'^' The abrupt shift of muscle metabolism, 

 on vigorous contraction, in just these directions, may. then, be due 

 to the fall in ATP concentration and this, in turn, to the movement of 

 ions to or from the critical enzyme surfaces. 



Another example of ion importance, especially of K+, is offered by 

 recent myosin studies. In an appropriate system, myosin B contracts 

 in 0.1 M KCl and relaxes when the K"" is doubled in concentration^*; 

 and an antagonism between K"^ and Ca*+, or Mg^^ and Ca""*, on myosin 

 action as ATP-ase and on myosin extension, has been repeatedly noted. 

 Potassium also increases the content of creatin phosphate in muscle 

 (while Ca"^"" decreases it),^"' •^"' ^" as well as of stable phosphate esters 

 in nerve,**^ perhaps by its ability to enhance CrP formation when 

 pyruvic acid is oxidized.''- This ion also aids both the synthesis and 

 the liberation of ACh and, conversely, ACh (or ATP) can release 



Tr+ 63, .55, 64 



It is not difficult to trace connections between these catalytic actions 

 of the tissue cations and the physiologic effects which ion changes pro- 



