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.
Hasegawa
Hiroshi
H
Department of Pathophysiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, 192-0392, Japan. hasegawa@ps.toyaku.ac.jp
Shinohara
Yoshihiko
Y
Akahane
Kenji
K
Hashimoto
Takao
T
Ichida
Kimiyoshi
K
D000818:Animals; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D003605:D-Amino-Acid Oxidase / Q000378:metabolism; D003903:Deuterium / Q000032:analysis; D008401:Gas Chromatography-Mass Spectrometry; D007275:Injections, Intravenous; D007553:Isotope Labeling; D007668:Kidney / Q000378:metabolism* / Q000601:surgery; D007700:Kinetics; D008297:Male; D008715:Methionine / Q000097:blood / Q000652:urine; D009392:Nephrectomy / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D008715:Methionine; D003903:Deuterium; D003404:Creatinine; D003605:D-Amino-Acid Oxidase