Altered d-methionine kinetics in rats with renal impairment

作者：Hasegawa Hiroshi^*; Shinohara Yoshihiko; Akahane Kenji; Hashimoto Takao; Ichida Kimiyoshi

来源：Amino Acids, 2011, 40(4): 1205-1211.

DOI：10.1007/s00726-010-0746-5

• D-Methionine
• Chiral inversion
• GC-MS
• Stable isotope
• 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-[(2)H(3)]methionine to 5/6-nephrectomized rats, plasma concentrations of d-[(2)H(3)]methionine, l-[(2)H(3)]methionine, and endogenous l-methionine were determined by a stereoselective GC-MS method. Renal mass reduction slowed down the elimination of d-[(2)H(3)]methionine. The clearance values of conversion of d-[(2)H(3)]methionine into the l-enantiomer in 5/6-nephrectomized rats were one-sixth of those in sham-operated rats. The elimination behavior of d-[(2)H(3)]methionine observed in rats demonstrated that kidney was the principal organ responsible for chiral inversion of d-methionine.

• 出版日期2011-4