Jacob C, Maret W, Vallee B L
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Seeley G. Mudd Building, 250 Longwood Avenue, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):1910-4. doi: 10.1073/pnas.96.5.1910.
Selenium has been increasingly recognized as an essential element in biology and medicine. Its biochemistry resembles that of sulfur, yet differs from it by virtue of both redox potentials and stabilities of its oxidation states. Selenium can substitute for the more ubiquitous sulfur of cysteine and as such plays an important role in more than a dozen selenoproteins. We have chosen to examine zinc-sulfur centers as possible targets of selenium redox biochemistry. Selenium compounds release zinc from zinc/thiolate-coordination environments, thereby affecting the cellular thiol redox state and the distribution of zinc and likely of other metal ions. Aromatic selenium compounds are excellent spectroscopic probes of the otherwise relatively unstable functional selenium groups. Zinc-coordinated thiolates, e.g., metallothionein (MT), and uncoordinated thiolates, e.g., glutathione, react with benzeneseleninic acid (oxidation state +2), benzeneselenenyl chloride (oxidation state 0) and selenocystamine (oxidation state -1). Benzeneseleninic acid and benzeneselenenyl chloride react very rapidly with MT and titrate substoichiometrically and with a 1:1 stoichiometry, respectively. Selenium compounds also catalyze the release of zinc from MT in peroxidation and thiol/disulfide-interchange reactions. The selenoenzyme glutathione peroxidase catalytically oxidizes MT and releases zinc in the presence of t-butyl hydroperoxide, suggesting that this type of redox chemistry may be employed in biology for the control of metal metabolism. Moreover, selenium compounds are likely targets for zinc/thiolate coordination centers in vivo, because the reactions are only partially suppressed by excess glutathione. This specificity and the potential to undergo catalytic reactions at low concentrations suggests that zinc release is a significant aspect of the therapeutic antioxidant actions of selenium compounds in antiinflammatory and anticarcinogenic agents.
硒在生物学和医学中日益被视为一种必需元素。它的生物化学性质与硫相似，但由于其氧化还原电位和氧化态稳定性的不同而与硫有所差异。硒可以替代半胱氨酸中更为常见的硫，因此在十几种硒蛋白中发挥着重要作用。我们选择研究锌 - 硫中心，将其作为硒氧化还原生物化学的可能靶点。硒化合物可从锌/硫醇盐配位环境中释放锌，从而影响细胞内硫醇的氧化还原状态以及锌的分布，可能还会影响其他金属离子的分布。芳香族硒化合物是其他相对不稳定的功能性硒基团的优良光谱探针。锌配位的硫醇盐，如金属硫蛋白（MT），以及未配位的硫醇盐，如谷胱甘肽，会与苯亚硒酸（氧化态 +2）、苯硒酰氯（氧化态 0）和硒代胱胺（氧化态 -1）发生反应。苯亚硒酸和苯硒酰氯与 MT 反应非常迅速，分别以亚化学计量和 1:1 的化学计量进行滴定。在过氧化和硫醇/二硫键交换反应中，硒化合物还能催化从 MT 中释放锌。硒酶谷胱甘肽过氧化物酶在叔丁基过氧化氢存在的情况下催化氧化 MT 并释放锌，这表明这种氧化还原化学作用可能在生物学中用于控制金属代谢。此外，硒化合物很可能是体内锌/硫醇盐配位中心的靶点，因为过量的谷胱甘肽只能部分抑制这些反应。这种特异性以及在低浓度下发生催化反应的潜力表明，锌的释放是硒化合物在抗炎和抗癌药物中发挥治疗性抗氧化作用的一个重要方面。
