Control Mechanism of the Formation of Neurotransmitter Monoamines by Pteridine Cofactor.
蝶啶辅因子形成神经递质单胺的控制机制。
基本信息
- 批准号:61540529
- 负责人:
- 金额:$ 1.09万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for General Scientific Research (C)
- 财政年份:1986
- 资助国家:日本
- 起止时间:1986 至 1987
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Tetrahydrobiopterin (BH_4) is an essential cofactor of aromatic amino acid hydroxylases such as tyrosine hydroxylase and tryptophan hydroxylase which are rate-limiting enzymes in the biosyntheses of catecholamine and indolamine. Thus the change in the concetration of BH_4 in the tissue effectively controls the formation of monoamines. (1)Some secretory functions of the rat salivary gland are regulated by the sympathetic nervous system. BH_4 in salivary glands of rate were meaured by HPLC method. An apparently constant biopterin concentration was observed in the gland, during the period after maturation in sympathetic innervation of the gland and the concentration of catecholamines behaved similarly. (2)Ret liver has quite high activity of sepiapterin reductase (SPR) which is an enzyme involved in the last step of the biosynthetic pathway of BH_4.SPR activity in rat liver was transiently stimulated by the injection of glucagon. This hormonal stimulation was quite similar, in time of maximal strimulation after injection, to that of hepatic phenylalanine hydroxylase which requires BH_4 as a confactor. (3)SPR acts as a NADPH-oxidoreductase against intermediates of keto-comound in BH_4 biosynthesis to form BH_4. Besides this activity, we found that SPR has an" isomerase activity" catalyzing the conversion of 6-lactoyl tetrahydropterin (Cl'-keto PH_4) into 6-1'-hydroxy-2'-oxopropyl tetrahydropterin (C2'-keto PH_4) which are both monoketo intermediates in the biosynthetic pathway of BH_4. It was also found that the new activity was stimulated by a small amount of NADP+ or NADPH. We postulated that reduction of pyruvoyl tetrahydropterin to BH_4 by SPR involves this isomerizing reaction in its sequential reaction; i.e., pyruvoyl tetrahydropterin ->[Cl'-keto PH_4 -> C2'-keto PH_4] -> BH_4. (4)Biosynthesis of BH_4 in animals or in reaction mechanism of its last step was summarized in our revies.
四氢生物蝶呤(BH_4)是酪氨酸羟化酶和色氨酸羟化酶等芳香族氨基酸羟化酶的重要辅助因子,而酪氨酸羟化酶和色氨酸羟化酶是儿茶酚胺和吲哚胺生物合成中的限速酶。因此,组织中BH_4浓度的变化有效地控制了单胺的形成。(1)大鼠唾液腺的一些分泌功能受交感神经系统的调节。用高效液相色谱法测定大鼠唾液腺中BH_4含量。在交感神经成熟后的一段时间内,在腺体中观察到明显恒定的生物蝶呤浓度,儿茶酚胺的浓度也有类似的变化。(2)Ret肝脏中参与BH_4生物合成最后一步的sepapterin reductase (SPR)活性较高。注射胰高血糖素可瞬间刺激大鼠肝脏SPR活性。在注射后的最大刺激时间,这种激素刺激与肝脏苯丙氨酸羟化酶的刺激非常相似,而苯丙氨酸羟化酶需要BH_4作为安慰剂。(3)在BH_4生物合成过程中,SPR作为nadph氧化还原酶对酮类化合物的中间体进行抑制,形成BH_4。此外,我们还发现SPR具有催化6-乳基四氢蝶呤(Cl'-keto PH_4)转化为6-1'-羟基-2'-氧丙基四氢蝶呤(C2'-keto PH_4)的异构酶活性,这两种酶都是BH_4生物合成途径中的单酮中间体。同时发现,少量NADP+或NADPH可刺激新活性。我们假设SPR还原丙酮酰四氢蝶呤为BH_4时,在其顺序反应中包含这个异构化反应;即丙酮基四氢蝶呤->[Cl′-酮PH_4 -> C2′-酮PH_4] -> BH_4。(4)综述了BH_4在动物体内的生物合成及其最后一步反应机理。
项目成果
期刊论文数量(30)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Katoh,S.;Sueoka,T.;Yamada,S.;Eds.B.A.Cooper;V.M.Whitehead: "Reversibility of α-Diketo Reductase Activity of Sepiapterin Reductase.in Chemistry and Biology of Pteridines 1986" Walter de Gruyter & Co.,Berlin,New York, 4(291-294) (1986)
Katoh, S.;Sueoka, T.;B. A. Cooper;V. M. Whitehead:“蝶啶的化学和生物学中的 α-二酮还原酶活性”,Walter de Gruyter & Co.,柏林,纽约,4(291-294) (1986)
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- 影响因子:0
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- 通讯作者:
Katoh, S.; Sueoka, T.; Yamada, S.: Reversibility of <alpha>-diketo reductase activity of sepiapterin reductase. In Chemistry and Biology of Pteridines (Cooper,B.A. & Whitehead,V.M.eds.). Walter de Gruyter Co., Berlin, New York, 291-294 (1986)
加藤,S.;
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Sueoka, T. ; Katoh, S.: "Reduction of biological quinones by sepiapterin reductase." Zool. Sci.3(6). 1011 (1986)
末冈,T.;
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- 影响因子:0
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Katoh,S;Akino,M.: Zoological Science. 3(5). 745-757 (1986)
Katoh,S;Akino,M.:动物学。
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- 影响因子:0
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KATOH Setsuko其他文献
KATOH Setsuko的其他文献
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{{ truncateString('KATOH Setsuko', 18)}}的其他基金
Signal transduction system in osteoclasts through tetrahydrobiopterin-mediated production of NO and cGMP.
破骨细胞中通过四氢生物蝶呤介导的 NO 和 cGMP 产生的信号转导系统。
- 批准号:
07672026 - 财政年份:1995
- 资助金额:
$ 1.09万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
相似海外基金
Expression analysis of the aldo-keto reductases involved in the novel biosynthetic pathway of tetrahydrobiopterin in human and mouse tissues
人和小鼠组织中参与四氢生物蝶呤新生物合成途径的醛酮还原酶的表达分析
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The novel biosynthetic pathway of tetrahydrobiopterin
四氢生物蝶呤的新型生物合成途径
- 批准号:
14570776 - 财政年份:2002
- 资助金额:
$ 1.09万 - 项目类别:
Grant-in-Aid for Scientific Research (C)