Studies on Arginine II. Phosphoarginine as a Possible Precursor of Creatine

Arginine was first suggested as the mother substance of creatine by Czernecki. From theoretical considerations the hypothesis has been generally regarded as an attractive one. It is in accordance with the fact that arginine, creatine and creatinine are the most abundant of the guanidine derivatives present in the animal organism. It is possible to postulate a series of plausible reactions by which the conversion of arginine to creatine might conceivably be accomplished. It is also in harmony with the mutually exclusive occurrence of arginine and creatine as demonstrated by Kutscher and Ackermann. These investigations have shown that creatine, a characteristic constituent of vertebrate muscle, is replaced by arginine in invertebrate muscle. Indeed the corresponding phospho esters, in which the muscle arginine and creatine largely occur, are even functionally equivalent., Nevertheless, efforts to demonstrate the origin of creatine from arginine have been unsuccessful, almost without exception. Numerous investigations, described in Hunter's monograph, and others referred to by Hyde and Rose have been entirely negative in result or open to serious criticism upon some crucial point. Doubtless one of the greatest difficulties in experiments in vivo has been the intervention of arginase, as a result of which administered arginine suffers rapid conversion to ornithine and urea. This competitive mechanism leaves little if any arginine available for the various reactions which are alleged to lead to creatine formation.