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Perturbation of Homeostasis by Enzymatic Depletion of blood Aromatic Amino Acid In Vivo and Its Metabolic?Physiological Consequences

Research Project

Project/Area Number 61480129
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Pathological medical chemistry
Research InstitutionFaculty of Medicine, The University of Tokyo

Principal Investigator

TAKAI Katsuji  Faculty of Medicine, The University of Tokyo, Professor, 医学部(医), 教授 (10010000)

Project Period (FY) 1986 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1987: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1986: ¥3,500,000 (Direct Cost: ¥3,500,000)
KeywordsHomeostasis / Aromatic Amino Acids / Tryptophan / Toyptophan Side Chain Oxidase / Serotonin / Brain Function / Sleep / Waking / 先行性アミノ酸代謝異常 / 酵素療法 / 血中アミノ酸パターン / カテコールアミン / 覚醒リズム
Research Abstract

In this study we dealt with the metabolic/physiological significance of the steady state levels of substrates/metabolites in vivo, as a quantitative representation of "homeostasis" in life. Rather than impairment of functional units of the system such as enzymes/recepotrs, we abopted an experimental approach of the negative perturbation (in contrast to positive perturbation alike loading) of the steady statev per se by admunistration of appropriate degrading enzymes specific for compound of out concern. level Concurrently, we assessed metabolic/physiological responses of the organs with special reference to their transient characteristic.
The first target was blood aromatic amino acids, precursors of neurotransmitters in brain, two of them being essential amino aeids To degrade phenylalaning/tyrosine we purified phenylalanine ammonialyase (PAL) and for tryptophan, tryptophan side chain oxidase 1 (TSO 1), both to homogeneity. The results taken together revealed that PAL depleted blood Ph … More e/Tyr efficiently followed by their decrease in brain, but no effect was found on catecholamine metabolism. This perturbation caused no change in amino acid pattern either in blood or brain, suggesting that these amino acids may be maintained constant in levels by a certain independent mechanism, and these level may notgserve as cues for the maintenance of amino acid pattern in vivo. On other hand, the steady state level of tryptophan was found to be crucial for brain functions/metabolism and also for maintenance of blood amino acid pattern. Concurrent with tryptophan depletion on administration of TSO 1, brain tryptophan simultaneously started to decrease followed by decrease in a neurotransmitter, serotonin. %-Hydroxyindole acetic acid(5-HIAA), an indicative of the serotonin neuron activity, also followd the time course of serotonin exactly. After several hours, serotonin-5-HIAA were reduced to 1/10 of the normal values representing that serotonin metabolism and serotonin neuron activity were virtually arrested simply bo restriction of an seeential amino acid in blood stream. Concurrent with this perturbation, sleep/waking pattern of rats were markedly changed;circadian rhythm was lost, and unique EEG appeared which likely represented a prototype of alternation of "consciousness.
Foregoing results clearyl indicated the presence of a system in which the steady state level of a blood constituent(other than fuels such as glucose or oxygen) couples with the brain function and thus the relevance of this kind of approach to homeostasis and its regulation in the whole body. Furthermore, these results opened a new perspective in central serotonin issues as yet not established. Less

Report

(2 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Katsuji TAKAI: Methods Enzymol. 142. 195-217 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 石田明: 脳と発達. 20. (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Katsuji TAKAI: The Fourth International Congress of Inborn Errors of Metabolism, May 27, Sendai, 1987, Abstr. p. 114. (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 高井克治: 生化学. 59. 661 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Katsuji TAKAI;Badway et al eds.: "Perturbations of Brain Serotonin(5-HT) Metabolism and Sleep/Waking Pattern of Rast by Enzymatic Depletion of Blood Tryptophan, in Progress in Tryptophan and Serotonin Research 1986" de Gruyter, Berlin, 75-77 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Katsuji TAKAI:Badawy et al. eds.: "The Mechanism of Dephydrogenation of Tryptophan Residues by Tryptophan Side Chain Oxidase II(TSO II), in Progress in Tryptophan and Serotonin Research 1986" de Cruyter, Berlin, 59-60 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Katsuji,Takai: "Purification and Properties of Tryptophan Side Chain Oxidase: Types I and II in Pseudomonas" Methods Enzymol.142. 195-217 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Akira,Ishida: "Serotonin Neuron Activity in Juvenile Parkinsonism" Brain and Development. 20. (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Katsuji,Takai: "Perturbations of Brain Serotonin (5-HT).Metabolism and Sleep/Waking Pattern of Rats by Enzymatic Depletion of Blood Tryptophan In Vivo" The Fourth International Congress of Inborn Errors of Metabolism, May 27, 1987 Sendai, Abstracts p. 114. (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Katsuji,Takai: "Perturbation of Serotonin(5-HT) Metabolism in the Central Nervous System by In Vivo Administration of Enzyme, and Its Metabolic/Physiological Consequences in Brain" Biochemistry(Seikagaku). 59(8). 661- (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Katsuji,Takai: Perturbations of Brain Serotonin(5-HT) Metabolism and Sleep/Waking Pattern of Rats by Enzymatic Depletion of Blood Tryptophan, in Progress in Tryptophan and Serotonin Research 1986, Badawy et al. eds. pp. 75-77, 1987, (75-77)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 高井克治: Methods,Enzymol.142. 195-217 (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 安井浩明: Proc.Nate.Acad.Sci.U.S.A.83. 6622-6626 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 石田明: 脳と発達. (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 高井克治: 生化学. 58. 847 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 高井克治: 生化学. 59. (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 薮下信: Astrophys.Space Sci.124. 377-388 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 高井克治 Badawy et al eds: "Perturbations of Brain Serotonin(5-HT),Wetabolisun and Sleep/Waking Potteru of Rats by Eunymatic Depletion of Blooa Tryptoplan:in Prog.Tryptopham and Serotouin Pes." De Gruyter,Berlin, (1987)

    • Related Report
      1986 Annual Research Report
  • [Publications] 高井克治 Badawy et al eds: "The Mechanism of Dehydrogenation of Tryptopham Residues by Tryptopham Siacchain Oridasc【II】(TSO【II】)from Psendomoues:in Prog,Tryptophan and Serotonic Res." De Gruyter,Berlin, (1987)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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