The present study addresses existing data on the affinity and conjugation of sulfhydryl (thiol; -SH) groups of low- and high-molecular-weight biological ligands with mercury (Hg). The consequences of these interactions with special emphasis on pathways of Hg toxicity are highlighted. Cysteine (Cys) is considered the primary target of Hg, and link its sensitivity with thiol groups and cellular damage. In vivo, Hg complexes play a key role in Hg metabolism. Due to the increased affinity of Hg to SH groups in Cys residues, glutathione (GSH) is reactive. The geometry of Hg(II) glutathionates is less understood than that with Cys. Both Cys and GSH Hg-conjugates are important in Hg transport. The binding of Hg to Cys mediates multiple toxic effects of Hg, especially inhibitory effects on enzymes and other proteins that contain free Cys residues. In blood plasma, albumin is the main Hg-binding (Hg²⁺, CH₃Hg⁺, C₂H₅Hg⁺, C₆H₅Hg⁺) protein. At the Cys₃₄ residue, Hg²⁺ binds to albumin, whereas other metals likely are bound at the N-terminal site and multi-metal binding sites. In addition to albumin, Hg binds to multiple Cys-containing enzymes (including manganese-superoxide dismutase (Mn-SOD), arginase I, sorbitol dehydrogenase, and δ-aminolevulinate dehydratase, etc.) involved in multiple processes. The affinity of Hg for thiol groups may also underlie the pathways of Hg toxicity. In particular, Hg-SH may contribute to apoptosis modulation by interfering with Akt/CREB, Keap1/Nrf2, NF-κB, and mitochondrial pathways. Mercury-induced oxidative stress may ensue from Cys-Hg binding and inhibition of Mn-SOD (Cys₁₉₆), thioredoxin reductase (TrxR) (Cys₄₉₇) activity, as well as limiting GSH (GS-HgCH₃) and Trx (Cys₃₂, ₃₅, ₆₂, ₆₅, ₇₃) availability. Moreover, Hg-thiol interaction also is crucial in the neurotoxicity of Hg by modulating the cytoskeleton and neuronal receptors, to name a few. However, existing data on the role of Hg-SH binding in the Hg toxicity remains poorly defined. Therefore, more research is needed to understand better the role of Hg-thiol binding in the molecular pathways of Hg toxicology and the critical role of thiols to counteract negative effects of Hg overload.

本研究涉及低分子量和高分子量生物配体的巯基（硫醇；-SH）基团与汞（Hg）的亲和力和缀合的现有数据。强调了这些相互作用的后果，特别强调汞毒性的途径。半胱氨酸 (Cys) 被认为是汞的主要靶标，并将其敏感性与硫醇基团和细胞损伤联系起来。在体内，汞复合物在汞代谢中发挥着关键作用。由于 Hg 对 Cys 残基中的 SH 基团的亲和力增加，谷胱甘肽 (GSH) 具有反应性。谷胱甘肽 Hg(II) 的几何形状比 Cys 的几何形状了解较少。Cys 和 GSH Hg 结合物在 Hg 转运中都很重要。Hg 与 Cys 的结合介导 Hg 的多种毒性作用，特别是对含有游离 Cys 残基的酶和其他蛋白质的抑制作用。在血浆中，白蛋白是主要的Hg结合蛋白（Hg ²⁺、CH ₃ Hg ⁺、C ₂ H ₅ Hg ⁺、C ₆ H ₅ Hg ⁺）蛋白。在 Cys ₃₄残基处，Hg ²⁺与白蛋白结合，而其他金属可能结合在 N 末端位点和多金属结合位点。除白蛋白外，Hg还与多种含半胱氨酸的酶（包括锰超氧化物歧化酶（Mn-SOD）、精氨酸酶I、山梨醇脱氢酶和δ-氨基乙酰丙酸脱水酶等）结合，参与多个过程。汞与硫醇基团的亲和力也可能是汞毒性途径的基础。特别是，Hg-SH 可能通过干扰 Akt/CREB、Keap1/Nrf2、NF-κB 和线粒体途径来调节细胞凋亡。汞诱导的氧化应激可能源自 Cys-Hg 结合和 Mn-SOD (Cys ₁₉₆ )、硫氧还蛋白还原酶 (TrxR) (Cys ₄₉₇ ) 活性的抑制，以及限制 GSH (GS-HgCH ₃ ) 和 Trx (Cys ₃₂ ) 、₃₅、₆₂、₆₅、₇₃）可用性。此外，汞-硫醇相互作用对于汞通过调节细胞骨架和神经元受体的神经毒性也至关重要。然而，关于汞-SH结合在汞毒性中的作用的现有数据仍然不明确。因此，需要更多的研究来更好地了解汞-硫醇结合在汞毒理学分子途径中的作用以及硫醇在抵消汞超载负面影响方面的关键作用。