Dietary supplementation with L-methionine impairs the utilization of urea-nitrogen and increases 5-L-oxoprolinuria in normal women consuming a low protein diet.

Urea kinetics were measured in normal women after 5 d consuming a low protein diet [LP, 67 mg N/(kg.d), 0.42 g protein/(kg.d)]. To determine whether the availability of methionine limits the utilization of nonessential nitrogen from low protein diets, the study was repeated on four further occasions with the addition of dietary supplements of L-methionine, 9 mg N/(kg.d) (LP-M); urea, 52 mg N/(kg.d) (LP-U); urea and methionine (LP-UM); or urea, 26 mg N/(kg.d), and glycine, 26 mg N/(kg.d), (LP-UG). Urea kinetics were derived after prime and intermittent oral doses of [15N15N]urea from the measurements of enrichment by isotope ratio mass spectrometry in urea isolated from urine. Nitrogen balance was significantly improved when the women consumed LP-U and LP-UG, but not LP-M or LP-UM. The urinary excretion of 5-L-oxoproline was measured as a marker of glycine availability and was significantly lower when women consumed LP-U and LP-UG compared with either LP or LP-M and LP-UM. There was a significant correlation between urinary 5-L-oxoproline and urinary sulfate excretion (r = 0.68, P = 0.00003). The availability of methionine was not limiting for nitrogen metabolism when women consumed these diets, whereas the response to supplementation with urea alone or urea with glycine showed that the availability of nonessential nitrogen was limiting. Glycine is consumed in the detoxification of excess methionine, and supplementation with methionine appeared to place a competitive demand on the availability of glycine for other metabolic processes.