The yellow color yielded by the Jaffe reaction, which is commonly employed for the determination of creatinine and creatine, is not highly specific and is ill-adapted to visual colorimetry. For the measurement of the comparatively gross quantities of creatinine and creatine excreted in the urine, it has proved quite accurate; but the small amounts of creatinine found in normal blood can be measured only with uncertainty. For creatine of serum, it has proved even more unsatisfactory than for creatinine. So slight is the increase in color produced by alkaline picrate after serum filtrates are exposed to acid and heat that the very presence of creatine in normal serum has been doubted (1 to 3). In the plasma of infants and of women who excreted creatine in the urine, Hunter and Campbell (1) and Wilson and Plass (2) detected appreciable increments of chromogenic material after treatment aimed to convert creatine to creatinine. This led them to the tentative conclusion that creatinuria marked the appearance of creatine in the serum of which it was not a normal component.Discouraged by these experiences, subsequent observers have confined their attentions to studies of the excretion of creatine in the urine, in which it appears in measurable quantities and without appreciable amounts of interfering chromogenic substances. Consequently, opinions about the metabolism of this substance, especially in human subjects, are largely based on inference. The recent presentation by Peters (4) of a procedure adapted to the Evelyn-Molloy photoelectric colorimeter has made it possible to measure creatine in serum with reasonable accuracy and therefore to examine the relation of creatinuria to the concentration of creatine in blood serum.The present paper deals with the mode of excretion of creatine by normal adults and the na-
METHODSBlood serum and urine were analyzed for creatinine and creatine by the Folin (5) method with the modifications devised by Peters (4) to adapt it to the Evelyn-Molloy photoelectric colorimeter. The most important of these are: (1) the use of a concentrated, but unsaturated solution of picric acid, containing 11.75 grams per liter instead of a saturated solution; and (2) the omission of hydrochloric acid as a dehydrating agent, since it was found that in tungstate filtrates, creatine is quantitatively converted to creatinine at autoclave temperature without the addition of acid. The error of the method does not exceed 0.1 mgm. per cent.Because of the variability of the concentrations of creatine and creatinine in urine, difficulty was at first experienced in bringing the color within the range of intensity suitable for the colorimeter. This was obviated by diluting all urines to a specific gravity of 1.010. From this diluted urine, a 1 to 20 dilution was made. This procedure brings the concentrations of creatine and creatinine regularly within the optimum colorimetric range.In a certain number of experiments, blood and urine were collected at approximately the same time, but the urine was not collected ...