Altered d-methionine kinetics in rats with renal impairment

d-Amino acids are now recognized to be widely present in mammals. In rats, exogenously administered d-methionine is almost converted into the l-enantiomer via 2-oxo-4-methylthiobutylic acid as an intermediate. d-Amino acid oxidase is associated with conversion of d-methionine into the 2-oxo acid. Since d-amino acid oxidase is present at the highest activity in the kidney compared to other organ, kidney injury is suggested to cause accumulation of d-methionine. The purpose of the present study is to assess the role of kidney in the elimination of d-methionine and metabolic conversion into l-methionine in rats using a stable isotope methodology. After a bolus i.v. administration of d-[2H3]methionine to 5/6-nephrectomized rats, plasma concentrations of d-[2H3]methionine, l-[2H3]methionine, and endogenous l-methionine were determined by a stereoselective GC–MS method. Renal mass reduction slowed down the elimination of d-[2H3]methionine. The clearance values of conversion of d-[2H3]methionine into the l-enantiomer in 5/6-nephrectomized rats were one-sixth of those in sham-operated rats. The elimination behavior of d-[2H3]methionine observed in rats demonstrated that kidney was the principal organ responsible for chiral inversion of d-methionine.