Tissue oxygen tension and brain sensitivity to hypoxia
Tissue oxygen tension and brain sensitivity to hypoxia
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DOI：
10.1016/s0034-5687(01)00306-1
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发表时间：
2001-11-15
期刊：
影响因子：
--
通讯作者：
Silver, IA
中科院分区：
文献类型：
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作者：
Erecinska, M;Silver, IA
哺乳动物的大脑是一个高度氧化的器官，虽然它只占总体重的一小部分，但它占身体耗氧量的比例不成比例地大（在人类中分别约为2%和20%）。然而，大脑中的氧分压和浓度低且不均匀。有大量的酶使用O-2作为底物，其中最重要的是细胞色素c氧化酶，这是线粒体ATP生产的关键。细胞色素c氧化酶对氧的亲和力非常高，这在正常条件下确保氧化磷酸化活性不降低到非常低的P-O2。相比之下，许多其他相关酶的氧Km值在周围脑气体张力之内或之上，因此使它们的操作非常依赖于生理范围内的氧水平。在其多种多样的功能中，氧分压和浓度控制活性氧的产生，基因的表达和离子通道的功能。限制氧气供应到大脑低于“临界”水平减少，并最终阻止氧化磷酸化，急剧减少细胞（ATP），并导致离子梯度的崩溃。神经元活动停止，如果不迅速重新引入氧气，细胞就会死亡。本文的目的是简要讨论哺乳动物脑的中枢氧依赖过程和缺氧的短期后果，而不是长期适应慢性缺氧的机制。特别强调的是，放在最近的关注和/或争议的焦点问题。(C)2001 Elsevier Science B. V.保留所有权利。
Mammalian brain is a highly oxidative organ and although it constitutes only a small fraction of total body weight it accounts for a disproportionately large percentage of bodily oxygen consumption (in humans about 2 and 20%, respectively). Yet, the partial pressure and concentration of oxygen in the brain are low and non-uniform. There is a large number of enzymes that use O-2 as a substrate, the most important of which is cytochrome c oxidase, the key to mitochondrial ATP production. The affinity of cytochrome c oxidase for oxygen is very high, which under normal conditions ensures undiminished activity of oxidative phosphorylation down to very low P-O2. By contrast, many other relevant enzymes have K-m values for oxygen within, or above, the ambient cerebral gas tension, thus making their operations very dependent on oxygen level in the physiological range. Among its multiple, versatile functions, oxygen partial pressure and concentration control production of reactive oxygen species, expression of genes and functions of ion channels. Limitation of oxygen supply to the brain below a 'critical' level reduces, and eventually blocks oxidative phosphorylation, drastically decreases cellular (ATP) and leads to a collapse of ion gradients. Neuronal activity ceases and if oxygen is not re-introduced quickly, cells die. The object of this review is to discuss briefly the central oxygen-dependent processes in mammalian brain and the short-term consequences of O-2 deprivation, but not the mechanisms of long-term adaptation to chronic hypoxia. Particular emphasis is-placed on issues which have been the focus of recent attention and/or controversy. (C) 2001 Elsevier Science B.V. All rights reserved.