Widespread neuronal expression of branched-chain aminotransferase in the CNS:: implications for leucine/glutamate metabolism and for signaling by amino acids
Widespread neuronal expression of branched-chain aminotransferase in the CNS:: implications for leucine/glutamate metabolism and for signaling by amino acids
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DOI：
10.1111/j.1471-4159.2006.04332.x
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发表时间：
2007-03-01
影响因子：
4.7
通讯作者：
Sweatt, Andrew J.
中科院分区：
文献类型：
--
作者：
García-Espinosa, María A.;Wallin, Reidar;Sweatt, Andrew J.
支链氨基酸的转氨作用产生谷氨酸和支链α - 酮酸。该反应由支链氨基转移酶（BCAT）催化，它存在胞质和线粒体异构体（BCATc和BCATm）。BCATc占大脑BCAT活性的70%，并且为谷氨酸合成提供至少30%所需的氮。在先前的研究中，我们发现BCATc存在于海马体和小脑中谷氨酸能神经元的突起以及γ - 氨基丁酸能神经元的胞体中。在此我们表明，这种代谢酶在整个大脑和脊髓中都有表达，在区域和细胞内的表达模式存在明显差异。在大脑皮层中，BCATc存在于γ - 氨基丁酸能中间神经元以及锥体细胞的轴突和近端树突中。BCATc的轴突标记延伸至胼胝体和内囊。基底神经节中的γ - 氨基丁酸能神经元以及下丘脑、中脑、脑干和背根神经节中的谷氨酸能神经元表达BCATc。BCATc还在下丘脑肽能神经元、脑干5 - 羟色胺能神经元和脊髓运动神经元中表达。结果表明，BCATc在一些区域积聚在神经元胞体中，而在其他区域则被运输到轴突和神经末梢。该酶能够影响多种神经元类型中的谷氨酸库。BCATc还可能使神经元对营养来源的支链氨基酸敏感，这在下丘脑弓状核等控制摄食行为的区域可能很重要，因为该区域的神经元高水平表达BCATc。
Transamination of the branched-chain amino acids produces glutamate and branched-chain alpha-ketoacids. The reaction is catalyzed by branched-chain aminotransferase (BCAT), of which there are cytosolic and mitochondrial isoforms (BCATc and BCATm). BCATc accounts for 70% of brain BCAT activity, and contributes at least 30% of the nitrogen required for glutamate synthesis. In previous work, we showed that BCATc is present in the processes of glutamatergic neurons and in cell bodies of GABAergic neurons in hippocampus and cerebellum. Here we show that this metabolic enzyme is expressed throughout the brain and spinal cord, with distinct differences in regional and intracellular patterns of expression. In the cerebral cortex, BCATc is present in GABAergic interneurons and in pyramidal cell axons and proximal dendrites. Axonal labeling for BCATc continues into the corpus callosum and internal capsule. BCATc is expressed by GABAergic neurons in the basal ganglia and by glutamatergic neurons in the hypothalamus, midbrain, brainstem, and dorsal root ganglia. BCATc is also expressed in hypothalamic peptidergic neurons, brainstem serotoninergic neurons, and spinal cord motor neurons. The results indicate that BCATc accumulates in neuronal cell bodies in some regions, while elsewhere it is exported to axons and nerve terminals. The enzyme is in a position to influence pools of glutamate in a variety of neuronal types. BCATc may also provide neurons with sensitivity to nutrient-derived BCAAs, which may be important in regions that control feeding behavior, such as the arcuate nucleus of the hypothalamus, where neurons express high levels of BCATc.