Fractional synthesis rate of creatine from arginine in healthy adult men

Creatine is synthesized from the amino acids arginine, glycine and methionine. We performed a study using 15 N 2 ‐guanidino arginine, to elucidate synthesis of creatine from dietary arginine in adult men. A primed, intermittent infusion of labeled 15 N 2 ‐guanidino arginine was given enterally to 5 healthy men fed a standardized milkshake diet. Blood was sampled at baseline and at plateau, between 1.5 and 3 hours. Enrichment of M+2 isotopomers of arginine, guanidino acetate (GAA), creatine and creatinine was measured by LC‐tandem MS. Plasma enrichment of the arginine tracer was 6.1 APE (Stdev ±1.05%), giving a flux estimate of 93 ìmol/kg/hr. M+2 isotopomers of creatine and GAA from the arginine tracer were detected in all subjects. There was no measurable M+2 creatinine. Enrichment of creatine was 0.55 APE (±0.1%) and GAA 4.92 APE (±0.8%). The fractional synthesis rate of GAA from arginine was 81% and 9% for creatine from arginine, these results are in keeping with synthesis of GAA being the rate limiting step in the creatine synthesis pathway. We have demonstrated synthesis of creatine from labeled dietary arginine in healthy adult humans; this method will allow in vivo studies in humans to directly measure synthesis rates of creatine. Supported by a grant from the CIHR.