The Function of Creatine in Muscular Contraction.

Abstract

INTRODUCTORY.It was in the investigations of Fick, carried out over fifty years ago, that the idea arose of two distinct chemical processes underlying the contraction and relaxation phases of a single muscle twitch. This conception, disregarded at the time, has during recent years been clearly established by the researches of Fletcher and Hopkins, of A. V. Hill, and of Meyerhof; and it is now quite certain that while contraction is caused by the liberation of lactic acid on to certain sensitive surfaces within the muscle fibres, relaxation occurs when this acid is again removed, not, indeed, by oxidation, as was for a time believed, but simplythrough neutralization by one of the basic substances contained in muscle.The work of Meyerhof (20) has made it appear probable that it is the muscle proteins that bring about this neutralization, the sodium salts of protein reacting with lactic acid to form sodium lactate and the very weakly dissociated acidprotein. The investigation has necessarily turned mainly about one point, namely, an attempt to correlate the heat of formation and neutralization of a given quantity of lactic acid in muscle, with the heat of formation and subsequent neutralization by protein buffers, of the same quantity of acid, when carried out in laboratory glassware. The formation of 1 gr. lactic acid in muscle is accompanied by the liberation of 370-410 calories (19,21), average about 389 calories (21). Combustion experiments on glycogen and lactic acid reveal a value of 188 cal. as the heat of formation of lactic acid from glycogen. During the neutralization of 1 gr. lactic acid by protein buffers of muscle about 140 cal. are produced. In his most recent work (21) Meyerhof believes that the remaining 60-70 calories are identical with the delayed anaerobic recovery heat of Hartree and Hill (12), and that dehydration of protein in a non-aquaeous phase underlies this recovery heat, and also the unexplained 60 to 70 calories.My own studies on the structure of muscle fibres have made it appear more probable that the neutralizing base is formed simultaneously with the lactic acid-

Phosphagen

“…of phosphagen P. One might expect the muscle in situ to be in phosphate equilibrium with the blood. It has been known for some time that a muscle placed in Ringer's solution loses both phosphate(Embden &Adler, 1922) and creatine (Tiegs, 1925) faster in a fatigued than in a resting state, and an increase in the blood phosphate of athletes after a short spell of violent exertion has been recorded by Harvard & Reay (1926), while Embden & Grafe (1921) report that there is an increased excretion of phosphate by the kidney during the performance. All the evidence seems to point to a free diffusibility of phosphate through the cell wall.…”

Creatine and Phosphocreatine in the Human Red Cell

“…It has been shown that when the red-cell membrane is destroyed by haemolysis the liberated creatine is capable of passing through a semi-permeable membrane. Tiegs (1925) observed that although creatine can be dialysed from fatigued frog's muscle into saline it does not diffuse from resting muscle, which led him to suggest that creatine exists in muscle in two forms, one diffusible and the other non-diffusible. This speculation was confirmed by the discovery of Eggleton and Eggleton (1927) of a non-diffusible compound of creatine which Fiske and Subbarow (1929) identified as phosphocreatine.…”

The diffusion of creatine and urea through muscle

“…Regarding creatine no information has been published since the work of Tiegs [1925] who showed that creatine diffuses from fatigued frog muscles into a saline solution, but not from resting, and that the admission of oxygen diminished diffusibility. He rightly supposed that creatine must exist in two forms in the muscle, the diffusible form predominating in the fatigued state.…”