Depletion of Cerebral D-Serine in Non-Ketotic Hyperglycinemia: Possible Involvement of Glycine Cleavage System in Control of Endogenous D-Serine

Iwama, Hiroshi; Takahashi, Katsunobu; Kure, Shigeo; Hayashi, Fumio; Narisawa, Kuniaki; Tada, Keiya; Mizoguchi, Masashi; Takashima, Sachio; Tomita, Urara; Nishikawa, Toru

doi:10.1006/bbrc.1997.6184

Cited by 53 publications

(36 citation statements)

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“…Although the involvement of the glycine cleavage system (GCS) (Iwama et al, 1997) or the hydrolysis of phosphoserine by phosphoserine phosphatase (Wood et al, 1996) in D-serine formation was suggested, the origin of D-serine in mammalian brain was largely unclear until the discovery of SR (Wolosker et al, 1999a,b). SR is a bifunctional enzyme that catalyzes the formation of D-serine and pyruvate (De Miranda et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

NMDA- and β-Amyloid_1–42-Induced Neurotoxicity Is Attenuated in Serine Racemase Knock-Out Mice

Inoue¹,

Hashimoto²,

Harai³

et al. 2008

J. Neurosci.

147

117

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Section: Discussionmentioning

confidence: 99%

NMDA- and β-Amyloid_1–42-Induced Neurotoxicity Is Attenuated in Serine Racemase Knock-Out Mice

Inoue¹,

Hashimoto²,

Harai³

et al. 2008

J. Neurosci.

147

117

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“…Indeed, substances including D-serine that act on the glycine site of the NMDA receptor influence schizophrenic symptoms 48) and their animal models, [1][2][3][4][5]49) cerebral ataxia, 50,51) the action of alcohol, 42) learning ability in dementia model animals, 42) anxiety behavior, 42) convulsion threshold, 42) ischemic neuron death, 42,52) and long-term behavioral abnormalities due to drug dependence. 42) A drastic reduction in the brain D-serine contents was found in patients with non-ketotic hyperglycinemia 34) lacking the glycine cleavage system who presented various central nervous symptoms such as mental retardation, convulsive attacks, apnea, and drowsiness. Particularly, attention has recently been directed to the possible association of endogenous D-serine with the pathophysiology of schizophrenia.…”

Section: )mentioning

confidence: 99%

Metabolism and Functional Roles of Endogenous D-Serine in Mammalian Brains

Nishikawa

2005

Biological & Pharmaceutical Bulletin

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“…The D-serine concentration was markedly reduced in the cortical tissues of three NKH patients as compared with the control tissues (Iwama et al, 1997). D-serine is the only D-amino acid ever studied that V\ f\/-"~-,, '-v"',,-..S ",./',._/ "".…”

Section: Neurological Basis Of Nkhmentioning

confidence: 86%

Nonketotic hyperglycinemia: Biochemical, molecular, and neurological aspects

1997

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SummaryNonketotic hyperglycinemia (NKH) is a metabolic disorder with autosomal recessive inheritance, causing severe, frequently lethal, neurological symptoms in the neonatal period. The metabolic lesion of NKH is in the glycine cleavage system (GCS), a complex enzyme system with four enzyme components; P-, T-, H-, and L-protein.The enzymatic analysis revealed that 86% of the patients with NKH are deficient of P-protein activity. The cDNA clones encoding all four components were isolated and their primary structures were determined. Several mutations have been identified in P-and T-protein genes: One missense mutation, $564I, in P-protein gene accounts for 70% of the mutant alleles in Finland where the incidence of NKH is unusually high. The immunochemical and in situ hybridization analyses revealed that the strong GCS expression was observed in rat hippocampus, olfactory bulbus, and cerebellum. The distribution resembled that of N-methyl-D-aspartic acid (NMDA) receptor which has binding site for glycine. It is, therefore, suggested that the neurological disturbance in NKH may be caused by excitoneurotoxicity through the NMDA receptor allosterically activated by high concentration of glycine. Based on the hypothesis the NMDA antagonists such as ketamine and dextromethorphan were administered to the patients. We treated three neonatal case with dextromethorphan and it ameliorated their findings on electroencephalogram and behavior in two out of three patients. Thus the GCS is suggested to play a role in regulation of glycine level around the NMDA receptor. In troductionNonketotic hyperglycinemia (NKH) is an autosomal recessive disorder of * To whom correspondence should be addressed.

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Depletion of Cerebral D-Serine in Non-Ketotic Hyperglycinemia: Possible Involvement of Glycine Cleavage System in Control of Endogenous D-Serine

Cited by 53 publications

References 18 publications

NMDA- and β-Amyloid_1–42-Induced Neurotoxicity Is Attenuated in Serine Racemase Knock-Out Mice

NMDA- and β-Amyloid_1–42-Induced Neurotoxicity Is Attenuated in Serine Racemase Knock-Out Mice

Metabolism and Functional Roles of Endogenous D-Serine in Mammalian Brains

Nonketotic hyperglycinemia: Biochemical, molecular, and neurological aspects

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Depletion of Cerebral D-Serine in Non-Ketotic Hyperglycinemia: Possible Involvement of Glycine Cleavage System in Control of Endogenous D-Serine

Cited by 53 publications

References 18 publications

NMDA- and β-Amyloid1–42-Induced Neurotoxicity Is Attenuated in Serine Racemase Knock-Out Mice

NMDA- and β-Amyloid1–42-Induced Neurotoxicity Is Attenuated in Serine Racemase Knock-Out Mice

Metabolism and Functional Roles of Endogenous D-Serine in Mammalian Brains

Nonketotic hyperglycinemia: Biochemical, molecular, and neurological aspects

Contact Info

Product

Resources

About

NMDA- and β-Amyloid_1–42-Induced Neurotoxicity Is Attenuated in Serine Racemase Knock-Out Mice

NMDA- and β-Amyloid_1–42-Induced Neurotoxicity Is Attenuated in Serine Racemase Knock-Out Mice