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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Intercellular metabolic compartmentation in the brain: past, present and future.
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Intercellular metabolic compartmentation in the brain: past, present and future.

机译：大脑中的细胞间代谢区室：过去，现在和将来。

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摘要

The first indication of 'metabolic compartmentation' in brain was the demonstration that glutamine after intracisternal [14C]glutamate administration is formed from a compartment of the glutamate pool that comprises at most one-fifth of the total glutamate content in the brain. This pool, which was designated 'the small compartment,' is now known to be made up predominantly or exclusively of astrocytes, which accumulate glutamate avidly and express glutamine synthetase activity, whereas this enzyme is absent from neurons, which eventually were established to constitute 'the large compartment.' During the following decades, the metabolic compartment concept was refined, aided by emerging studies of energy metabolism and glutamate uptake in cellularly homogenous preparations and by the histochemical observations that the two key enzymes glutamine synthetase and pyruvate carboxylase are active in astrocytes but absent in neurons. It is, however, only during the last few years that nuclear magnetic resonance (NMR) spectroscopy, assisted by previously obtained knowledge of metabolic pathways, has allowed accurate determination in the human brain in situ of actual metabolic fluxes through the neuronal tricarboxylic acid (TCA) cycle, the glial, presumably mainly astrocytic, TCA cycle, pyruvate carboxylation, and the 'glutamate-glutamine cycle,' connecting neuronal and astrocytic metabolism. Astrocytes account for 20% of oxidative metabolism of glucose in the human brain cortex and accumulate the bulk of neuronally released transmitter glutamate, part of which is rapidly converted to glutamine and returned to neurons in the glutamate-glutamine cycle. However, one-third of released transmitter glutamate is replaced by de novo synthesis of glutamate from glucose in astrocytes, suggesting that at steady state a corresponding amount of glutamate is oxidatively degraded. Net degradation of glutamate may not always equal its net production from glucose and enhanced glutamatergic activity, occurring during different types of cerebral stimulation, including the establishment of memory, may be associated with increased de novo synthesis of glutamate. This process may contribute to a larger increase in glucose utilization rate than in rate of oxygen consumption during brain activation. The energy yield in astrocytes from glutamate formation is strongly dependent upon the fate of the generated glutamate.
机译：大脑中“代谢区隔”的第一个迹象是证实，脑池内[14C]谷氨酸给药后的谷氨酰胺是由谷氨酸池的一个部分形成的，该部分最多占大脑总谷氨酸含量的五分之一。现在已知该池被称为“小隔间”，主要或仅由星形胶质细胞组成，这些星形胶质细胞会大量累积谷氨酸并表达谷氨酰胺合成酶活性，而神经元中则不存在这种酶，最终被证实构成“大隔间。在随后的几十年中，通过对细胞均质制剂中能量代谢和谷氨酸吸收的新兴研究以及组织化学观察的结果，即对两种关键酶谷氨酰胺合成酶和丙酮酸羧化酶在星形胶质细胞中有活性，但在神经元中却没有这种活性的研究，完善了代谢区室的概念。但是，仅在最近几年中，借助先前获得的代谢途径知识，核磁共振（NMR）光谱才可以在人脑中准确确定通过神经元三羧酸（TCA）的实际代谢通量。 ）周期，神经胶质（主要是星形细胞），TCA周期，丙酮酸羧化和“谷氨酸-谷氨酰胺循环”（连接神经元和星形细胞代谢）。在人类大脑皮层中，星形胶质细胞占葡萄糖氧化代谢的20％，并累积大量神经元释放的递质谷氨酸，其中一部分迅速转化为谷氨酰胺并在谷氨酸-谷氨酰胺循环中返回神经元。然而，释放的递质谷氨酸的三分之一被星形胶质细胞中葡萄糖的谷氨酸从头合成所取代，这表明在稳态下，相应量的谷氨酸被氧化降解。谷氨酸的净降解可能并不总是等于其从葡萄糖中产生的净产量，而且在不同类型的大脑刺激（包括建立记忆）中发生的增强的谷氨酸能活性可能与谷氨酸的从头合成增加有关。与大脑激活过程中的氧气消耗速率相比，此过程可能有助于更大程度地提高葡萄糖利用率。来自谷氨酸形成的星形胶质细胞的能量产量强烈取决于所产生的谷氨酸的命运。

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