Depletion of cerebral D-serine in non-ketotic hyperglycinemia: Possible involvement of glycine cleavage system in control of endogenous D-serine

Hisayuki Iwama, Katsunobu Takahashi, Shigeo Kure, Fumihiko Hayashi, Kuniaki Narisawa, Keiya Tada, Masashi Mizoguchi, Sachio Takashima, Urara Tomita, Toru Nishikawa

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46 Citations (Scopus)

Abstract

Tissue concentrations of D-serine and other chiral and non-chiral amino acids were measured post-mortem in the cerebral cortex of the neonatal or infantile individuals with (three cases) or without (seven cases) non-ketotic hyperglycinemia (NKH) using high performance liquid chromatography with fluorometric detection. In the cortical tissues of the NKH patients lacking activity of glycine cleavage system, there was a marked reduction and elevation of the contents of D-serine and glycine, respectively, compared to nonNKH controls. Systemic administration of an inhibitor of glycine cleavage system (GCS), cysteamine, mimicked the changes in the cortical concentrations of these amino acids in the 8-day-old rats. Augmentation of brain glycine levels by means of intraperitoneal inj ection of glycine itself resulted in an increase in cortical D-serine contents in the neonatal rats with normal activity of GCS. These findings provide the first evidence that GCS might be implicated in the biosynthesis or content regulation of endogenous D-serine in the mammalian brain.

Original languageEnglish
Pages (from-to)793-796
Number of pages4
JournalBiochemical and biophysical research communications
Volume231
Issue number3
DOIs
Publication statusPublished - 1997 Feb 24

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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