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On the physiological and cellular homeostasis of ascorbate.
Cellular & Molecular Biology Letters ( IF 8.3 ) Pub Date : 2020-05-29 , DOI: 10.1186/s11658-020-00223-y
Magdalena Przybyło 1, 2 , Marek Langner 1, 2
Affiliation  

Recent interest in the role of ascorbate in crucial metabolic processes is driven by the growing number of medical reports that show beneficial effects of ascorbate supplementation for maintaining general well-being and recovery from a variety of medical conditions. The effect of ascorbate on the local body environment highly depends on its local concentration; at low concentrations it can cause the reduction of reactive oxygen and facilitate activities of enzymes, while at high concentrations it generates free radicals by reducing ferric ions. Ascorbate serving as an electron donor assists the iron-containing proteins and the iron transfer between various aqueous compartments. These functions require effective and adjustable mechanisms responsible for ascorbate biodistribution. In the paper we propose a new biophysical model of ascorbate redistribution between various aqueous body compartments. It combines recent experimental evidence regarding the ability of ascorbate to cross the lipid bilayer by unassisted diffusion, with active transport by well-characterized sodium vitamin C transporter (SVCT) membrane proteins. In the model, the intracellular concentration of ascorbate is maintained by the balance of two opposing fluxes: fast active and slow passive transport. The model provides a mechanistic understanding of ascorbate flux across the epidermal barrier in the gut as well as the role of astrocytes in ascorbate recycling in the brain. In addition, ascorbate passive diffusion across biological membranes, which depends on membrane electric potentials and pH gradients, provides the rationale for the correlation between ascorbate distribution and the transfer of iron ions inside a cell. The proposed approach provides, for the first time, a mechanistic account of processes leading to ascorbate physiological and cellular distribution, which helps to explain numerous experimental and clinical observations.

中文翻译:

对抗坏血酸的生理和细胞动态平衡。

越来越多的医学报告引起了人们对抗坏血酸在关键代谢过程中的作用的最新兴趣,这些报告显示出补充抗坏血酸对维持各种疾病的总体健康和恢复有益的作用。抗坏血酸对当地人体环境的影响在很大程度上取决于其局部浓度。在低浓度下,它会引起活性氧的减少并促进酶的活性;而在高浓度下,它会通过还原铁离子而产生自由基。用作电子供体的抗坏血酸盐有助于含铁蛋白和铁在各种水性隔室之间的转移。这些功能需要有效和可调节的机制来负责抗坏血酸的生物分布。在本文中,我们提出了一种新的抗坏血酸在各个水体腔室之间重新分布的生物物理模型。它结合了有关抗坏血酸通过无助扩散穿过脂质双层的能力的实验证据,以及通过特征明确的维生素C钠转运蛋白(SVCT)膜蛋白进行的主动转运的能力。在该模型中,抗坏血酸的细胞内浓度通过两个相对通量的平衡来维持:快速主动运输和缓慢被动运输。该模型提供了对肠道中表皮屏障中抗坏血酸通量的机械理解,以及星形胶质细胞在大脑中抗坏血酸循环中的作用。此外,抗坏血酸在生物膜上的被动扩散取决于膜的电势和pH梯度,提供了抗坏血酸分布与细胞内铁离子转移之间相关性的原理。所提出的方法首次提供了导致抗坏血酸的生理和细胞分布的过程的机制解释,这有助于解释许多实验和临床观察。
更新日期:2020-07-24
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