The creatine-creatinine equilibrium. The apparent dissociation constants of creatine and creatinine

Abstract

THE facile conversion of creatine into creatinine under the influence of strong acids and the partial reversal of the reaction in neutral and in alkaline solutions have long been familiar.Yet only recently has there become available any quantitative data upon the equilibrium conditions.Hahn and Barkan [1920] were the first to report any systematic kinetic studies.They determined the equilibrium constant in solutions of sodium hydroxide of varying concen- tration, observed that the component velocities increased with increasing [OH-] and showed that the order of the reaction creatinine->creatine, under these conditions, was that of a reversible monomolecular system.In a molar solution of hydrochloric acid, on the other hand, the reverse reaction went to completion and followed the course of a simple monomolecular change.Hahn and Meyer [1923] later reported a few observations which indicated that the velocity of this reaction in buffered solutions increased rapidly from PH 6 to 4. A more elaborate study of this system has been made by Edgar and his associates.Edgar and Wakefield [1923] determined the monomolecular velocity constants (k2) of the dehydration of creatine in hydrochloric acid solutions of varying concentration and at various temperatures.They succeeded in relating k2 to the temperature by means of the Arrhenius equation and, further, concluded that k2 was, probably, proportional to the hydrogen ion activity.Finally, Edgar and Shiver [1925] have made an extensive series of determinations of the equilibrium constant (K) at 50° in buffered solutions of PH values 1 to 6. Hahn and Barkan had suggested that their observations could be interpreted upon the assumption that the molecular species whose concentrations deter- mined the equilibrium were the undissociated molecules of creatine and of creatinine.Confirming this, Edgar and Shiver obtained fairly satisfactory agreement between the observed values of K and those calculated from the dissociation constants of the two bases and the value of K in unbuffered solu- tion (i.e.where the two reactants were not significantly dissociated).