Department of Biochemistry, Kansas City University of Medicine and Biosciences, Kansas City, MO, USA.
Adv Exp Med Biol. 2013;985:269-91. doi: 10.1007/978-94-007-4716-6_9.
Thus far, two independent laboratories have shown that inhaled anesthetics directly affect GAPDH structure and function. Additionally, it has been demonstrated that GAPDH normally regulates the function of GABA (type A) receptor. In light of these literature observations and some less direct findings, there is a discussion on the putative role of GAPDH in anesthesia. The binding site of inhaled anesthetics is described from literature reports on model proteins, such as human serum albumin and apoferritin. In addition to the expected hydrophobic residues that occupy the binding cavity, there are hydrophilic residues at or in very close proximity to the site of anesthetic binding. A putative binding site in the bacterial analog of the human GABA (type A) receptor is also described. Additionally, GAPDH may also play a role in anesthetic preconditioning, a phenomenon that confers protection of cells and tissues to future challenges by noxious stimuli. The central thesis regarding this paradigm is that inhaled anesthetics evoke an intra-molecular protein dehydration that is recognized by the cell, eliciting a very specific burst of chaperone gene expression. The chaperones that are implicated are associated with conferring protection against dehydration-induced protein aggregation.
到目前为止，已有两个独立实验室表明吸入麻醉剂可直接影响 GAPDH 的结构和功能。此外，已经证明 GAPDH 通常可调节 GABA（A 型）受体的功能。鉴于这些文献观察结果和一些不太直接的发现，人们对 GAPDH 在麻醉中的可能作用进行了讨论。从人血清白蛋白和脱铁铁蛋白等模型蛋白的文献报告中描述了吸入麻醉剂的结合位点。除了占据结合腔的预期疏水性残基外，在麻醉剂结合部位或非常接近该部位处还有亲水性残基。还描述了人类 GABA（A 型）受体细菌类似物中的假定结合位点。此外，GAPDH 也可能在麻醉预处理中发挥作用，麻醉预处理是一种现象，它使细胞和组织对有害刺激的未来挑战具有保护作用。该范例的中心论点是，吸入麻醉剂会引起分子内蛋白质脱水，从而被细胞识别，引发伴侣蛋白表达的特定爆发。所涉及的伴侣蛋白与对脱水诱导的蛋白质聚集的保护有关。
