Combined 1H and 31P NMR studies of the rat brain in vivo: effects of altered intracellular pH on metabolism.
Combined 1H and 31P NMR studies of the rat brain in vivo: effects of altered intracellular pH on metabolism.
复制标题
大鼠脑体内 1H 和 31P NMR 联合研究：细胞内 pH 值改变对代谢的影响。
DOI：
10.1111/j.1749-6632.1987.tb32896.x
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发表时间：
1987
影响因子：
5.2
通讯作者：
Shulman,RG
中科院分区：
文献类型：
--
作者：
Behar,KL;Rothman,DL;Fitzpatrick,SM;Hetherington,HP;Shulman,RG
持续的细胞内酸中毒可导致脑代谢物浓度和周转率的显著变化。氢离子参与几种接近平衡的酶催化反应（如肌酸磷酸激酶、乳酸脱氢酶等）。因此，与这些反应相关的底物的稳态浓度可以根据[H +]而变化。[H +]的变化也可能通过代谢途径影响速率。pH对组织葡萄糖利用的影响已被广泛研究。在稳态条件下，低细胞内pH降低葡萄糖利用率，而细胞内pH升高葡萄糖利用率。3 - 5这些效应归因于[H +]对磷酸果糖-1-激酶活性的影响。"有人认为，低pHi可能有助于在缺血一段时间后再循环后葡萄糖摄取率降低。然而，[H +]对缺血期间糖酵解速率的影响与稳态下发生的糖酵解速率之间可能存在差异。例如，在缺血性肌肉的运动期间，酸化（由于乳酸的糖酵解产生）持续到低至6.0的细胞内pH值。9 pH值的变化也对TCA循环中间体和通过转氨酶和脱氢酶与TCA循环相连的氨基酸的浓度产生显著影响。"在酸碱变化过程中，这些有机酸阴离子的稳态浓度的变化被认为是实现细胞内pH的一种手段。决定这些变化的方向和幅度的pH敏感位点是未知的;了解它们的位置将有助于更好地理解氨基酸水平在导致细胞酸中毒的条件下是如何改变的。由于二氧化碳容易通过血脑屏障转运，从而诱导细胞内酸中毒。CO沿着其浓度或分压梯度的扩散决定了进入或离开脑细胞的净运动。因此，血液中CO2张力的变化将导致脑组织CO2张力的平行变化。在细胞内C0的水合和快速解离之后，由碳酸酐酶的高催化活性辅助的-H+被释放，根据下式降低pHi：
A sustained intracellular acidosis may lead to marked changes in the concentrations and turnover rates of cerebral metabolites. Hydrogen ions participate in several enzyme-catalyzed reactions operating near equilibrium (eg, creatine phosphokinase, lactate dehydrogenase, etc.). Therefore, the steady-state concentrations of substrates linked to these reactions could change according to [H+]. Changes in [H+] may also affect rates through metabolic pathways. The effects of pH on tissue glucose utilization have been studied e~ tensively.'-~ Under steady-state conditions, low intracellular pH decreases glucose utilization, whereas intracellular alkalosis enhances it. 3-5 These effects are ascribed to an influence of [H+] on the activity of phosphofructo-1-kina~ e.~" It has been suggested that low pHi may contribute to the depressed rates of glucose uptake following recirculation after a period of ischemia.'Differences may exist, however, between the effects of [H+] on the glycolytic rate during ischemia and that occurring in the steady state. For example, during exercise in ischemic muscle, acidification (due to glycolytic production of lactic acid) persists to intracellular pH values as low as 6.0. 9 Changes in pH also have a dramatic effect on the concentrations of TCA cycle intermediates and amino acids linked to the TCA cycle through aminotransferases and dehydrogenases." Changes in the steady-state concentrations of these organic acid anions during acidlbase changes has been proposed as a means of achieving intracellular pH The pH-sensitive site (s) that determine the direction and magnitude of these changes are unknown; knowledge of their location would lead to a better understanding of how amino acid levels are altered for those conditions leading to cellular acidosis.Hypercarbia is an efficient means of inducing intracellular acidosis as carbon dioxide is easily transported through the blood-brain barrier. The diffusion of CO, along its concentration or partial-pressure gradient determines net movement into or out of brain cells. Variations in CO, tensions in blood will lead, therefore, to parallel changes in brain tissue C 0 2 tensions. Following the hydration and rapid dissociation of intracellular C0,-assisted by the high catalytic activity of carbonic anhydrase-H+ is liberated, lowering the pHi according to: