Depletion of cerebral D-serine in non-ketotic hyperglycinemia: possible involvement of glycine cleavage system in control of endogenous D-serine.
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 non-NKH 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 injection 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.
Iwama
H
H
Department of Mental Disorder Research, National Institute of Neuroscience, NCNP, Tokyo, Japan.
Takahashi
K
K
Kure
S
S
Hayashi
F
F
Narisawa
K
K
Tada
K
K
Mizoguchi
M
M
Takashima
S
S
Tomita
U
U
Nishikawa
T
T
D000594:Amino Acid Oxidoreductases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003543:Cysteamine / Q000494:pharmacology; D005998:Glycine / Q000097:blood* / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D051381:Rats; D012694:Serine / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D014166:Transferases / Q000378:metabolism
D002352:Carrier Proteins; D009097:Multienzyme Complexes; C064525:glycine cleavage system; D012694:Serine; D003543:Cysteamine; D000594:Amino Acid Oxidoreductases; D014166:Transferases; D005998:Glycine