Translational Enzymology on D-Amino Acid Metabolizing System in the Brain Controlled by Vitamin B

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  • Fukui Kiyoshi
    Department of Enzyme Pathophysiology, Institute for Enzyme Research, University of Tokushima

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Other Title
  • ビタミンB群が担う脳内D-アミノ酸代謝システムの疾患酵素学研究(<特集>ビタミンB研究委員会平成25年度シンポジウム「ビタミンB群が担う脳内アミノ酸代謝と疾患をターゲットにした次世代学術研究-ビタミン研究が切り拓く疾患生命科学のフロンティア」)
  • ビタミンB群が担う脳内D-アミノ酸代謝システムの疾患酵素学研究
  • ビタミン Bグン ガ ニナウ ノウナイ D-アミノサン タイシャ システム ノ シッカン コウソガク ケンキュウ

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Description

D-Amino acid oxidase (DAO) is a flavoenzyme that catalyses the oxidative deamination of D-amino acids. D-Serine, one of the physiological substrates for DAO, is an endogenous co-agonist for N-methyl D-aspartate (NMDA) receptor and plays important roles in glutamate receptor-mediated neurotransmission. Based on the enzymatic activity of DAO in D-serine catabolism, the enzyme has been proposed to be involved in the decreased glutamatergic neurotransmission in schizophrenia. Therefore, the modulation of DAO activity is expected to be useful for the therapy of schizophrenia. We examined the inhibitory effect of antipsychotic drugs, chlorpromazine and risperidone, on human DAO activity and demonstrated that chlorpromazine and risperidone inhibited the enzyme activity. Moreover, we examined the distribution of DAO in brain to clarify its pathophysiological role in the regulation of neurotransmission. Immunohistochemcal analyses revealed that DAO was present in glial cells and choroid plexus (CP) in human brain. The level of DAO expression in CP epithelial cells in schizophrenic patients was also found to be significantly higher than the normal control. These results indicate the possibility that a decrease in D-serine concentration due to an increase in DAO expressed in CP epithelial cells in brain is involved in the pathophysiology of schizophrenia which is caused by dysfunction of NMDA receptor. From these findings, it can be thought that DAO expressed in CP is regarded as a potential therapeutic target for schizophrenia and also it can be expected that a new therapeutic agent for schizophrenia will be developed.

Journal

  • VITAMINS

    VITAMINS 88 (10), 524-529, 2014

    THE VITAMIN SOCIETY OF JAPAN

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