Altered D: -methionine kinetics in rats with renal impairment

Amino Acids. 2011 Apr;40(4):1205-11. doi: 10.1007/s00726-010-0746-5. Epub 2010 Sep 25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Creatinine / blood
  • D-Amino-Acid Oxidase / metabolism
  • Deuterium / analysis
  • Gas Chromatography-Mass Spectrometry
  • Injections, Intravenous
  • Isotope Labeling
  • Kidney / metabolism*
  • Kidney / surgery
  • Kinetics
  • Male
  • Methionine* / blood
  • Methionine* / urine
  • Nephrectomy / adverse effects
  • Rats
  • Rats, Sprague-Dawley
  • Stereoisomerism

Substances

  • Methionine
  • Deuterium
  • Creatinine
  • D-Amino-Acid Oxidase