Expression of mitochondrial branched-chain aminotransferase and α-keto-acid dehydrogenase in rat brain: implications for neurotransmitter metabolism.
Expression of mitochondrial branched-chain aminotransferase and α-keto-acid dehydrogenase in rat brain: implications for neurotransmitter metabolism.
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DOI：
10.3389/fnana.2012.00018
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发表时间：
2012
影响因子：
2.9
通讯作者：
Hutson SM
中科院分区：
文献类型：
--
作者：
Cole JT;Sweatt AJ;Hutson SM
在大脑中，必需支链氨基酸（BCAA）亮氨酸、异亮氨酸和缬氨酸的代谢部分受蛋白质合成需求的调节。过量的BCAA被分解代谢或排出体外。支链氨基酸催化的第一步是由支链氨基转移酶（BCAT）同工酶，线粒体BCATm和胞质BCATc催化。这种反应的产物谷氨酸是主要的兴奋性神经递质，也是主要的抑制性神经递质γ-氨基丁酸（GABA）的前体。BCAT被认为参与α-酮-酸氮穿梭，为从α-酮戊二酸合成谷氨酸提供氮。支链α-酮酸脱氢酶复合物（BCKDC）催化BCAA代谢中的第二个不可逆步骤，即BCAT反应的支链α-酮酸（BCKA）产物的氧化脱羧。枫糖浆尿病（MSUD）是由BCKDC的遗传缺陷引起的，这导致BCAA和BCKAs的毒性水平的积累，导致脑肿胀。大鼠中BCATm和BCKDC的免疫定位显示，BCATm存在于白色物质中的星形胶质细胞和神经胶质细胞中，而BCKDC仅在神经元中表达。BCATm似乎均匀分布在整个大脑的星形胶质细胞体中。BCATm向星形胶质细胞的分离和BCKDC向神经元的分离为BCAA依赖性神经胶质-神经元氮穿梭的存在提供了进一步的支持，因为数据显示由神经胶质BCATm产生的BCKAs必须输出到神经元。此外，BCKDC的神经元定位表明，MSUD是一种神经元缺陷，涉及BCKAs氧化不足，继发性效应超出神经元。
In the brain, metabolism of the essential branched chain amino acids (BCAAs) leucine, isoleucine, and valine, is regulated in part by protein synthesis requirements. Excess BCAAs are catabolized or excreted. The first step in BCAA catabolism is catalyzed by the branched chain aminotransferase (BCAT) isozymes, mitochondrial BCATm and cytosolic BCATc. A product of this reaction, glutamate, is the major excitatory neurotransmitter and precursor of the major inhibitory neurotransmitter γ-aminobutyric acid (GABA). The BCATs are thought to participate in a α-keto-acid nitrogen shuttle that provides nitrogen for synthesis of glutamate from α-ketoglutarate. The branched-chain α-keto acid dehydrogenase enzyme complex (BCKDC) catalyzes the second, irreversible step in BCAA metabolism, which is oxidative decarboxylation of the branched-chain α-keto acid (BCKA) products of the BCAT reaction. Maple Syrup Urine Disease (MSUD) results from genetic defects in BCKDC, which leads to accumulation of toxic levels of BCAAs and BCKAs that result in brain swelling. Immunolocalization of BCATm and BCKDC in rats revealed that BCATm is present in astrocytes in white matter and in neuropil, while BCKDC is expressed only in neurons. BCATm appears uniformly distributed in astrocyte cell bodies throughout the brain. The segregation of BCATm to astrocytes and BCKDC to neurons provides further support for the existence of a BCAA-dependent glial-neuronal nitrogen shuttle since the data show that BCKAs produced by glial BCATm must be exported to neurons. Additionally, the neuronal localization of BCKDC suggests that MSUD is a neuronal defect involving insufficient oxidation of BCKAs, with secondary effects extending beyond the neuron.
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影响因子：
56.9
作者：
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通讯作者：
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DOI：
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发表时间：
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影响因子：
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