The hydrolysis of phosphocreatine and the origin of urinary creatinine.

Xhaffer (1)) Myers and Fine (2), and Hahn and Meyer (3) adduced evidence that muscle creatine is the precursor of urinary creatinine. This was questioned by Chanutin and Kinard (4) but was conclusively proved by Bloch, Schoenheimer, and Rittenberg (5, 6) by isotope tracer evidence, which also showed that creatinine was the only normal urinary constituent containing any significant amount of body creatine nitrogen.’ Although Bloch, Schoenheimer, and Rittenberg had settled the issue of the relation between creatine and creatinine, the site and mechanism of creatinine formation and the place of phosphocreatine in the process were still open questions. The crux of all three questions is the fact that the amount of creatinine normally excreted is greater than can be accounted for by the spontaneous (i.e., non-enzymatic) rate of dehydration of creatine at the pH and temperature of the body. Thus Myers and Fine (7) found that the creatine in finely ground muscle was transformed to creatinine more than 3 times as fast as in pure solutions of creatine. Hammett (8) measured the velocity constants of the transformation at 38” and pH 6.9 of the creatine in buffered extracts of rat brain and muscle and in similarly buffered solutions of pure creatine. The velocity constants in the brain suspensions ranged from 0.00083 to 0.00148, average 0.00117; in muscle 0.00091 to 0.00119, average 0.00104; and in creatine solutions 0.00058. (The time unit of these constants is 1 hour.) The percentage of creatine converted in 24 hours calculated from these constants was, in the brain and muscle extracts, 2.8, and in the creatine solution 1.4. The rate of conversion of creatine to creatinine in viva is of the same order of magnitude as observed by Hammett in brain and in muscle extracts. Table I is an assembly of the data obtained by direct observation on this point.2