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天冬氨酸转氨酶活性和酮二羧酸载体功能对于递质谷氨酸的生物合成至关重要的证据。

Evidence that aspartate aminotransferase activity and ketodicarboxylate carrier function are essential for biosynthesis of transmitter glutamate.

作者信息

Palaiologos G, Hertz L, Schousboe A

机构信息

Department of Biochemistry A, Panum Institute, University of Copenhagen, Denmark.

出版信息

J Neurochem. 1988 Jul;51(1):317-20. doi: 10.1111/j.1471-4159.1988.tb04872.x.

DOI:10.1111/j.1471-4159.1988.tb04872.x
PMID:2898006
Abstract

Based on the selective inhibition of glutamate release in cerebellar granule cells in primary cultures by the aspartate aminotransferase inhibitor, aminooxyacetic acid, and by the ketodicarboxylate carrier inhibitor, phenylsuccinate, a novel model for synthesis of transmitter glutamate is suggested: Glutamate is formed from glutamine in the mitochondrial intramembrane space by phosphate-activated glutaminase, transported across the inner membrane in exchange with aspartate, transaminated in the matrix to alpha-ketoglutarate, which via the ketodicarboxylate carrier is transferred to the cytoplasm, and transaminated to form transmitter glutamate. Such a mechanism would explain the functional role of aspartate aminotransferase in glutamatergic neurons.

摘要

基于天冬氨酸转氨酶抑制剂氨氧基乙酸以及酮二羧酸载体抑制剂苯基琥珀酸对原代培养的小脑颗粒细胞中谷氨酸释放的选择性抑制作用,提出了一种新型的递质谷氨酸合成模型:谷氨酸由谷氨酰胺在线粒体内膜间隙通过磷酸激活的谷氨酰胺酶形成,与天冬氨酸交换后穿过内膜转运至基质,在基质中转氨基生成α-酮戊二酸,α-酮戊二酸通过酮二羧酸载体转运至细胞质,再转氨基形成递质谷氨酸。这样一种机制将解释天冬氨酸转氨酶在谷氨酸能神经元中的功能作用。

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Evidence that aspartate aminotransferase activity and ketodicarboxylate carrier function are essential for biosynthesis of transmitter glutamate.天冬氨酸转氨酶活性和酮二羧酸载体功能对于递质谷氨酸的生物合成至关重要的证据。
J Neurochem. 1988 Jul;51(1):317-20. doi: 10.1111/j.1471-4159.1988.tb04872.x.
2
Role of aspartate aminotransferase and mitochondrial dicarboxylate transport for release of endogenously and exogenously supplied neurotransmitter in glutamatergic neurons.天冬氨酸转氨酶和线粒体二羧酸转运在谷氨酸能神经元中内源性和外源性供应神经递质释放中的作用。
Neurochem Res. 1989 Apr;14(4):359-66. doi: 10.1007/BF01000039.
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Utilization of alpha-ketoglutarate as a precursor for transmitter glutamate in cultured cerebellar granule cells.在培养的小脑颗粒细胞中,利用α-酮戊二酸作为递质谷氨酸的前体。
Neurochem Res. 1991 Jan;16(1):29-34. doi: 10.1007/BF00965824.
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Hyperammonemic alterations in the metabolism of glutamate and aspartate in rat cerebellar astrocytes.大鼠小脑星形胶质细胞中谷氨酸和天冬氨酸代谢的高氨血症改变
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Aspartate aminotransferase for synthesis of transmitter glutamate in the medulla oblongata: effect of aminooxyacetic acid and 2-oxoglutarate.天冬氨酸转氨酶参与延髓中神经递质谷氨酸的合成:氨基氧乙酸和2-氧代戊二酸的作用。
J Neurochem. 1989 Apr;52(4):1127-34. doi: 10.1111/j.1471-4159.1989.tb01857.x.
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Effectors of D-[3H]aspartate release from rat cerebellum.大鼠小脑释放D-[3H]天冬氨酸的效应物。
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Ontogenetic development of glutamate metabolizing enzymes in cultured cerebellar granule cells and in cerebellum in vivo.培养的小脑颗粒细胞和体内小脑中谷氨酸代谢酶的个体发育。
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Glutamine as a precursor for transmitter glutamate, aspartate and GABA in the cerebellum: a role for phosphate-activated glutaminase.谷氨酰胺作为小脑中转录物谷氨酸、天冬氨酸和γ-氨基丁酸的前体:磷酸激活谷氨酰胺酶的作用。
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Evidence using in vivo microdialysis that aminotransferase activities are important in the regulation of the pools of transmitter amino acids.
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Re-activation by glutamate or aspartate of amino-oxyacetate-inhibited aspartate aminotransferase in vitro and in isolated hepatocytes.谷氨酸或天冬氨酸在体外及分离的肝细胞中对氨基氧乙酸抑制的天冬氨酸转氨酶的再激活作用。
Biochem J. 1981 Jul 15;198(1):219-23. doi: 10.1042/bj1980219.

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