Methylglyoxal, the dark side of glycolysis.
Methylglyoxal, the dark side of glycolysis.
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DOI：
10.3389/fnins.2015.00023
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发表时间：
2015
影响因子：
4.3
通讯作者：
Magistretti PJ
中科院分区：
文献类型：
--
作者：
Allaman I;Bélanger M;Magistretti PJ
葡萄糖是大脑的主要能量基质。现在有大量的证据表明，神经细胞在葡萄糖利用和糖酵解速率方面的代谢谱是不均匀的，与神经元相比，星形胶质细胞中糖酵解葡萄糖加工的倾向明显。丙酮醛是一种高活性的二羰基化合物，不可避免地作为糖酵解的副产物形成。丙酮醛是糖基化终产物（AGEs）的主要细胞渗透前体，与糖尿病、衰老和神经退行性疾病等多种病理学相关。在正常情况下，通过不同的机制保护细胞免受甲基乙二醛毒性，特别是代表甲基乙二醛解毒的最重要途径的谷胱甘肽酶系统。虽然丙酮醛和AGEs的神经毒性作用得到了很好的表征，但我们对大脑中的谷胱甘肽酶系统的理解更为分散。考虑到高能量需求（即，葡萄糖），人们应该预期大脑的谷胱甘肽酶系统足以处理甲基乙二醛毒性。这篇综述着重于我们对脑细胞中的谷胱甘肽酶系统的细胞方面的实际知识，特别是关于其在星形胶质细胞和神经元中的活性。一个主要的新兴概念是，这两种神经细胞类型具有不同的和积极适应的glycoprotein酶防御机制，这可能是对甲基glycoprotein诱导的细胞损伤的保护机制。
Glucose is the main energy substrate for the brain. There is now extensive evidence indicating that the metabolic profile of neural cells with regard to glucose utilization and glycolysis rate is not homogenous, with a marked propensity for glycolytic glucose processing in astrocytes compared to neurons. Methylglyoxal, a highly reactive dicarbonyl compound, is inevitably formed as a by-product of glycolysis. Methylglyoxal is a major cell-permeant precursor of advanced glycation end-products (AGEs), which are associated with several pathologies including diabetes, aging and neurodegenerative diseases. In normal situations, cells are protected against methylglyoxal toxicity by different mechanisms and in particular the glyoxalase system, which represents the most important pathway for the detoxification of methylglyoxal. While the neurotoxic effects of methylglyoxal and AGEs are well characterized, our understanding the glyoxalase system in the brain is more scattered. Considering the high energy requirements (i.e., glucose) of the brain, one should expect that the cerebral glyoxalase system is adequately fitted to handle methylglyoxal toxicity. This review focuses on our actual knowledge on the cellular aspects of the glyoxalase system in brain cells, in particular with regard to its activity in astrocytes and neurons. A main emerging concept is that these two neural cell types have different and energetically adapted glyoxalase defense mechanisms which may serve as protective mechanism against methylglyoxal-induced cellular damage.