The glutathione dependence of inorganic sulfate formation from L- or D-cysteine in isolated rat hepatocytes
The glutathione dependence of inorganic sulfate formation from L- or D-cysteine in isolated rat hepatocytes
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DOI：
10.1016/s0009-2797(98)00015-5
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发表时间：
1998-04-03
影响因子：
5.1
通讯作者：
O'Brien, PJ
中科院分区：
文献类型：
--
作者：
Huang, J;Khan, S;O'Brien, PJ
完整细胞中半胱氨酸转化为硫酸盐所涉及的代谢途径对谷胱甘肽的依赖性已被研究。研究发现，如果肝细胞内 GSH 事先耗尽，则添加的 L-半胱氨酸不会发生肝细胞催化的硫酸盐形成，但当 GSH 水平恢复时又会恢复。此外，如果用丁硫氨酸亚磺酰亚胺阻止 GSH 合成，则 GSH 耗尽的肝细胞中的硫酸盐形成不会恢复。然而，在GSH耗尽的肝细胞中，硫代硫酸盐的形成显着增强。这些结果表明，硫代硫酸盐是L-半胱氨酸形成无机硫酸盐的中间体，并且GSH是硫代硫酸盐转化为无机硫酸盐所必需的。如果将半胱氨酸替换为半胱亚磺酸盐，则形成的硫酸盐要少得多。此外，添加转氨酶抑制剂DL-环丝氨酸或γ-胱硫醚酶抑制剂DL-炔丙基甘氨酸显着抑制了L-半胱氨酸的硫酸盐形成。因此，L-半胱氨酸形成硫酸盐的主要途径似乎涉及不涉及L-半胱亚磺酸盐的途径。 D-半胱氨酸形成的硫酸盐量与L-半胱氨酸相似。在谷胱甘肽耗尽的肝细胞中也形成硫代硫酸盐而不是硫酸盐。然而，D-半胱氨酸形成的硫酸盐与L-半胱氨酸不同，它受到D-氨基酸氧化酶抑制剂苯甲酸钠的抑制，并且不受转氨酶或γ-胱硫醚酶抑制剂的影响。这些结果表明硫代硫酸盐是D-半胱氨酸形成硫酸盐的中间体，并且涉及D-氨基酸氧化酶将D-半胱氨酸氧化形成β-巯基丙酮酸。 (C) 1998 Elsevier Science Ireland Ltd. 保留所有权利。
The GSH dependence of the metabolic pathways involved in the conversion of cysteine to sulfate in intact cells has been investigated. It was found that hepatocyte-catalysed sulfate formation from added L-cysteine did not occur if hepatocyte GSH was depleted beforehand, but was restored when GSH levels recovered. Furthermore, sulfate formation did not recover in GSH-depleted hepatocytes if GSH synthesis was prevented with buthionine sulfoximine. Thiosulfate formation was, however, markedly enhanced in GSH-depleted hepatocytes, These results suggest that thiosulfate is an intermediate in the formation of inorganic sulfate from L-cysteine and that GSH was required for the conversion of thiosulfate to inorganic sulfate. Much less sulfate was formed if the cysteine was replaced with cysteinesulfinate. Furthermore, sulfate formation from L-cysteine was markedly inhibited by the addition of the transaminase inhibitor DL-cycloserine or the gamma-cystathionase inhibitor DL-propargyl-glycine. The major routes of sulfate formation from L-cysteine therefore seems to involve pathways that do not involve L-cysteinesulfinate. Similar amounts of sulfate were formed from D-cysteine as L-cysteine. Thiosulfate instead of sulfate was also formed in GSH-depleted hepatocytes. However, sulfate formation from D-cysteine differed from L-cysteine in that it was inhibited by the D-amino acid oxidase inhibitor sodium benzoate and was not affected by transaminase or gamma-cystathionase inhibitors. These results suggest that thiosulfate is an intermediate in sulfate formation from D-cysteine and involves the oxidation of D-cysteine by D-amino acid oxidase to form beta-mercaptopyruvate. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.