Thermodynamic stoichiometry of Na+-coupled glutathione transport.
Thermodynamic stoichiometry of Na+-coupled glutathione transport.
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Na偶联谷胱甘肽运输的热力学化学计量。
DOI：
10.1139/y06-067
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发表时间：
2006
影响因子：
2.1
通讯作者：
Kannan,Ram
中科院分区：
文献类型：
--
作者：
Gukasyan,HovhannesJ;Lee,VincentHL;Simityan,Hagop;Kim,Kwang-Jin;Kannan,Ram
关于谷胱甘肽（GSH）转运的机制和GSH转运蛋白的分子身份存在着歧义。经验和理论的局限性阻碍了功能和分子表征。已发表的文献中提到的Na+-耦合GSH转运介导的细胞摄取的GSH的分离和分子鉴定是高度争议。而一些功能和动力学的报告，这种假定的共转运机制存在，假设的跨膜Na+耦合GSH转运蛋白或编码它的遗传信息尚未被隔离。理论热力学计算，以支持二级主动GSH运输的概念，并合理化帐户的物理动力学测量描述Na+耦合细胞GSH摄取进行。所需的能量和化学计量守恒的单独的电气和化学成分的Na+梯度在保持高细胞的GSH积累梯度的充分性进行了研究，通过一个纯粹的现象学的角度。根据生物背景，能量耦合之间的Na+和GSH共转运可能发生在1：1至3：1的比例。负责细胞Na+-耦合GSH摄取的特定转运蛋白的分子鉴定将有助于确定其对整体质膜静息电位的相对贡献。在GSH浓度相对于其细胞外微环境较高的组织中，特别是在囊性纤维化和干眼综合征的病理中，可预期Na+和GSH共转运的能量耦合比较大。Na+偶联GSH转运可能在疾病发作和（或）进展或其治疗方式中起重要作用。
Ambiguity exists with respect to mechanisms of glutathione (GSH) transport and the molecular identity of GSH transporters. Empirical and theoretical limitations have hindered functional and molecular characterizations. Published literature referring to the isolation and molecular identification of Na+-coupled GSH transporters that mediate the cellular uptake of GSH is highly debated. Whereas a number of functional and kinetic reports of this putative symport mechanism exist, the hypothetical transmembrane Na+-coupled GSH transporter protein or the genetic message encoding it has not been isolated. Theoretical thermodynamic calculations to support the concept of secondary active GSH transport and to rationalize accounts of physical-kinetic measurements describing Na+-coupled cellular GSH uptake were performed. The adequacy of requisite energy and stoichiometric conservation of the separate electrical and chemical components of a Na+gradient in maintaining a high cellular accumulation gradient for GSH was examined through a purely phenomenological perspective. Dependent on the biological context, the energetic coupling between Na+and GSH cotransport may occur at ratios from 1:1 to 3:1. Molecular identification of specific transporters responsible for cellular Na+-coupled GSH uptake will facilitate determination of their relative contribution to the overall plasma membrane resting potential. In tissues with a high GSH concentration relative to their extracellular millieu, particularly in pathologies of cystic fibrosis and dry eye syndromes, large energy coupling ratios in cotransport of Na+and GSH may be expected. Na+-coupled GSH transport may play an important role in disease onset and (or) progression, or treatment modalities thereof.