Tanabe Shinzo
Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose City, Japan.
Yakugaku Zasshi. 2008 Jun;128(6):881-900. doi: 10.1248/yakushi.128.881.
Inorganic sulfur compounds, such as S(2-), SO(3)(2-) and S(2)O(3)(2-), are produced from sulfur- containing amino acids as intermediary metabolites in mammalian tissues through complex pathways and are ultimately incorporated into sulfate. Reduced sulfur is also produced via the desulfuration of cysteine by several sulfurtransferases present in mammalian tissues; these enzymes include gamma-cystathionase (gamma-CST), and 3-mercaptopyruvate sulfurtransferase (3-MST). This reduced sulfur is then incorporated into pools of active reduced sulfur (sulfane sulfur; polysulfides, polythionates, thiosulfate, thiosulfonates and elemental sulfur) that are involved in the detoxication of cyanide and in the biosynthesis of iron-sulfur cluster. Sulfane sulfur is labile and is reduced to H(2)S by reducing agents. The physiological function of these sulfur species is less clear. We have found that a reduced sulfur species is commonly present in mammalian sera and tissues as a high molecular weight material and as both a high and a low molecular weight material, respectively; we designated this sulfur species as "bound sulfur." Bound sulfur can be easily liberated as sulfide by reduction with DTT. This review describes sensitive and specific assay method for determining the presence of inorganic sulfur compounds as well as bound sulfur and related sulfurtransferases in biological samples. The physiological functions of bound sulfur in rat tissues were also evaluated using these assay methods. Bound sulfur was found to be located primarily in the rat liver cytosolic fraction in the form of high molecular weight components. The capacity of bound sulfur production was enriched in the cytosol fraction and depended on gamma-CST. Bound sulfur also affected redox regulation by modifying active thiol residues in some liver cytosol enzymes and effectively inhibited cytochrome P-450-dependent lipid peroxidation induced by CCl(4) and t-BuOOH.
无机硫化合物，如S(2-)、SO(3)(2-)和S(2)O(3)(2-)，作为含硫氨基酸在哺乳动物组织中的中间代谢产物，通过复杂途径产生，最终被整合到硫酸盐中。还原态硫也可通过哺乳动物组织中几种硫转移酶对半胱氨酸的脱硫作用产生；这些酶包括γ-胱硫醚酶（γ-CST）和3-巯基丙酮酸硫转移酶（3-MST）。然后，这种还原态硫被整合到活性还原态硫（硫烷硫；多硫化物、连多硫酸盐、硫代硫酸盐、硫代磺酸盐和元素硫）池中，这些硫参与氰化物的解毒和铁硫簇的生物合成。硫烷硫不稳定，可被还原剂还原为H(2)S。这些硫物种的生理功能尚不清楚。我们发现，一种还原态硫物种通常以高分子量物质以及分别以高分子量和低分子量物质的形式存在于哺乳动物血清和组织中；我们将这种硫物种称为“结合硫”。结合硫可通过用二硫苏糖醇（DTT）还原而轻易地以硫化物形式释放出来。本综述描述了用于测定生物样品中无机硫化合物以及结合硫和相关硫转移酶存在的灵敏且特异的检测方法。还使用这些检测方法评估了结合硫在大鼠组织中的生理功能。发现结合硫主要以高分子量成分的形式位于大鼠肝脏胞质部分。结合硫的产生能力在胞质部分中富集，并且依赖于γ-CST。结合硫还通过修饰一些肝脏胞质酶中的活性巯基残基来影响氧化还原调节，并有效抑制由四氯化碳（CCl(4)）和叔丁基过氧化氢（t-BuOOH）诱导的细胞色素P-450依赖性脂质过氧化。
