Studies on the Metabolism of Creatine and Creatinine Iii. Formation of Creatine by Isolated Rat Tissues*

The precursors, mechanism, and site of creatine formation are still uncertain, even though they have received the attention of investigators for many years. An examination of the results on creatine formation summarized in Hunter’s monograph (1928) shows the many contradictions in this field. In the 10 years which have elapsed since the publication of this work, few experiments in vivo have been performed which clarify the problem. On the other hand, several workers have reported recently the synthesis of creatine by tissues in vitro. The observations of Borsook and Jeffreys (1935) indicate that creatine is formed by liver, kidney, diaphragm, and intestine, and that the rate of formation can be increased in liver by the addition of a complete hydrolysate of egg albumin. Fisher and Wilhelmi (1937) observed an increase in creatine after perfusing the isolated rabbit heart with arginine. Bach (1939) reported an apparent increase in creatine after incubation of chopped rat heart with glycocyamine and glycine. The specificity of the methods employed in the above investigations is open to some question. We present in this communication results on creatine formation by rat tissues in vitro, obtained by employing the specific, enxymatic method of Miller, Allinson, and Baker (1939) for the estimation of creatine. The capacity of various tissues to form creatine, without addition of possible precursors, has been observed.