Studies on metabolisms of paralytic shellfish toxins in scallop in association with the reductive transformation by thiols

有毒甲藻如亚历山大藻引起的麻痹性贝类中毒。是最突出的贝类毒素，因其症状剧烈，致死率高。一旦被麻痹性贝类毒素污染，双壳贝类的毒素净化需要一段时间。由于这种现象，贝类市场长期关闭，对贝类产业造成严重损害。然而，由于对毒素的代谢规律知之甚少，目前还没有有效的方法去除双壳贝类中的麻痹性贝类毒素。膝沟藻毒素（GTXs）是链霉菌毒素（STX）的11-O-硫酸酯衍生物，是亚历山大藻属（Alexandiumspp.）分布于北方太平洋海域。有毒甲藻水华期间贝类的毒素概况反映了致病甲藻的毒素概况。然而，在甲藻消失后的毒素降解期，贝类的毒素谱逐渐发生变化，如部分GTX转化为STXs，但其转化的生物学过程尚未阐明。最近，我们发现细菌提取物可将GTX转化为STXs。在这种转化中，发现提取物中的谷胱甘肽（GSH）参与其中。在反应过程中形成GSH和STX的稳定缀合物。这些结果表明，贝类组织中的GSH参与了GTXs向STXs的转化，并在贝类体内形成和积累了GS-STXs结合物。然而，在滋补贝类中没有检测到缀合物，这表明缀合物上发生了一些事情。在这项研究中，我们证明，STXs部分的GS-STXs共轭物被分解时，谷氨酸残基被释放的g-谷氨酰转肽酶，表明GSH也参与GTX的分解积累在贝类。

Paralytic shellfish poisoning caused by toxic dinoflagellates such as Alexandrium spp. is the most prominent shell poison because of acuteness of the symptoms and high fatality. Once contaminated by paralytic shellfish toxins, it takes a time to depurate toxins in bivalves. A long-time closure of the shellfish market due to this phenomenon poses severe damage to the shellfish industry. However, no effective method to remove paralytic shellfish toxins from bivalves have been developed, because there is little knowledge about the metabolism of the toxins. Gonyautoxins (GTXs), 11-O-sulfate derivatives of STX, are major components of Alexandrium spp. which distribute in northern Pacific area. Toxin profile of the shellfish during a bloom of toxic dinoflagellates reflects that of the causative dinoflagellate. In the toxin deputation period after disappearance of the causative dinoflagellates, however, toxin profile of the shellfish gradually changes, for example, a part of GTXs transforms to STXs, though the biological process of transformation has not been elucidated. Recently, we have found that bacterial extracts transform GTXs to STXs. In this transformation, glutathione (GSH) in the extract is found to be involved. A stable conjugate of GSH and STXs is formed in a process of the reaction. These findings suggest that GSH in the shellfish tissue is involved in the transformation of GTXs to STXs of the shellfish during deputation period, and that GS-STXs conjugates are formed and accumulated in the shellfish. However, the conjugates were not detected in the tonic shellfish, suggesting that something happens on the conjugates. In this study, we demonstrate that STXs moiety of the GS-STXs conjugates are decomposed when glutamic acid residue is released by g-glutamyltranspeptidase, indicating that GSH is involved also in decomposition of GTXs accumulated in the shellfish.