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Department of Pathophysiology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 14321 Horinouchi, Hachioji, Tokyo 192-0392, Japan
2To whom correspondence should be addressed. E-mail: hasegawa{at}ps.toyaku.ac.jp.
The stereoselective kinetics of methionine enantiomers in rats was investigated to evaluate the fraction that converted from D-methionine to the L-enantiomer using a stable isotope methodology. After bolus i.v. administration of D- or L-[2H3]methionine, their plasma concentrations and that of endogenous L-methionine were determined by a stereoselective GC-MS method. L-[2H3]Methionine appeared rapidly after administration of D-[2H3]methionine, whereas D-[2H3]methionine was not detected after administration of L-[2H3]methionine. The fraction of conversion of D-[2H3]methionine into L-[2H3]methionine was estimated using the area under the plasma concentration vs. time curve of L-[2H3]methionine on D-[2H3]methionine administration and total clearance of L-[2H3]methionine on L-[2H3]methionine administration, and that fraction was >90%. This result demonstrates that almost all i.v. administered D-methionine is converted into the L-enantiomer in vivo.
KEY WORDS: D-methionine chiral inversion GC-MS stable isotope D-amino-acid oxidase