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Altered d-methionine kinetics in rats with renal impairment

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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.

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Abbreviations

AUCl(←d) :

AUC of l-amino acid formed from d-amino acid

CL:

Clearance

CLd→l :

The metabolic clearance associated with conversion of d-amino acid into the l-enantiomer

F d→l :

Fraction of conversion of d-amino acid into the l-enantiomer

MTPA:

α-Methoxy-α-trifluoromethyl-phenylacetyl

OMe:

Methyl ester

Nx:

Nephrectomy

SIM:

Selected ion monitoring

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Acknowledgments

This work was supported in part by grants from the Japan Private School Promotion Foundation and the Science Research Promotion Fund, The Promotion and Mutual Aid Corporation for Private Schools of Japan.

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Authors and Affiliations

  1. Department of Pathophysiology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan

    Hiroshi Hasegawa, Yoshihiko Shinohara, Kenji Akahane, Takao Hashimoto & Kimiyoshi Ichida

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  1. Hiroshi Hasegawa
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  2. Yoshihiko Shinohara
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  3. Kenji Akahane
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  4. Takao Hashimoto
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  5. Kimiyoshi Ichida
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Correspondence to Hiroshi Hasegawa.

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Hasegawa, H., Shinohara, Y., Akahane, K. et al. Altered d-methionine kinetics in rats with renal impairment. Amino Acids 40, 1205–1211 (2011). https://doi.org/10.1007/s00726-010-0746-5

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  • DOI: https://doi.org/10.1007/s00726-010-0746-5

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