Brain is well known for its disproportionate oxygen consumption and high energy-budget for optimal functioning. The decrease in oxygen supply to brain, thus, necessitates rapid activation of adaptive pathways - the absence of which manifest into vivid pathological conditions. Amongst these, oxygen sensing in glio-vascular milieu and H2S-dependent compensatory increase in cerebral blood flow (CBF) is a major adaptive response. We had recently demonstrated that the levels of H2S were significantly decreased during chronic hypobaric hypoxia (HH)-induced neuro-pathological effects. The mechanistic basis of this phenomenon, however, remained to be deciphered. We, here, describe experimental evidence for marked limitation of cysteine during HH - both in animal model as well as human volunteers ascending to high altitude. We show that the preservation of brain cysteine level, employing cysteine pro-drug (N-acetyl-L-cysteine, NAC), markedly curtailed effects of HH - not only on endogenous H2S levels but also, impairment of spatial reference memory in our animal model. We, further, present multiple lines of experimental evidence that the limitation of cysteine was causally governed by physiological propensity of brain to utilize cysteine, in cystathionine beta synthase (CBS)-dependent manner, past its endogenous replenishment potential. Notably, decrease in the levels of brain cysteine manifested despite positive effect (up-regulation) of HH on endogenous cysteine maintenance pathways and thus, qualifying cysteine as a conditionally essential nutrient (CEN) during HH. In brief, our data supports an adaptive, physiological role of CBS-mediated cysteine-utilization pathway - activated to increase endogenous levels of H2S - for optimal responses of brain to hypobaric hypoxia.

中文翻译：

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半胱氨酸在低压缺氧过程中成为有条件的必需物质，并通过CBS / H2S途径调节适应性神经生理反应。

大脑以其不均衡的氧气消耗和高能量预算来实现最佳功能而闻名。因此，向大脑供氧的减少需要迅速激活适应性途径-缺乏适应性途径会表现出生动的病理状况。其中，胶质-血管环境中的氧气感测和H2S依赖性的脑血流量（CBF）补偿性增加是主要的适应性反应。我们最近证明，在慢性低压缺氧（HH）诱导的神经病理学效应期间，H2S的水平显着降低。但是，这种现象的机理基础尚待破译。在这里，我们描述了在HH期间半胱氨酸显着受限的实验证据-在动物模型以及升至高海拔的人类志愿者中都如此。我们表明，使用半胱氨酸前药（N-乙酰-L-半胱氨酸，NAC）来保存脑半胱氨酸水平，显着降低了HH的影响-不仅对内源性H2S水平，而且还损害了我们动物体内的空间参考记忆模型。我们进一步提供了多行实验证据，证明半胱氨酸的局限性是由大脑的生理倾向性决定的，该生理倾向是通过胱硫醚β合酶（CBS）依赖性方式利用半胱氨酸，超过了其内源性补充潜力。值得注意的是，尽管HH对内源性半胱氨酸维持途径有积极作用（上调），但脑半胱氨酸水平却有所降低，因此，在HH期间将半胱氨酸定为有条件的必需营养素（CEN）。简而言之，我们的数据支持自适应，