生体内含硫無機化合物の定量法並びにイオウ転移酵素の測定法の開発と,結合型イオウの生理学的機能評価

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タイトル別名
  • Development of Assay Methods for Endogenous Inorganic Sulfur Compounds and Sulfurtransferases and Evaluation of the Physiological Functions of Bound Sulfur
  • セイタイナイ ガンリュウ ムキ カゴウブツ ノ テイリョウホウ ナラビニ イオウ テンイ コウソ ノ ソクテイホウ ノ カイハツ ト ケツゴウガタ イオウ ノ セイリガクテキ キノウ ヒョウカ

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  Inorganic sulfur compounds, such as S2−, SO32− and S2O32−, 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 γ-cystathionase (γ-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 H2S 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, respectvively; 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 γ-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 CCl4 and t-BuOOH.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 128 (6), 881-900, 2008-06-01

    公益社団法人 日本薬学会

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