维持细胞内铜离子浓度稳定的分子机制

The Mechanism of Copper Tolerance

对生命而言，铜是一种必须的微量元素，它以辅基的形式参与细胞内多种重要的代谢途径。赖氨酸氧化酶参与结缔组织的形成和胶原交联，超氧化物歧化酶清除胞内自由基，细胞色素氧化酶是呼吸链电子传送蛋白，酪氨酸酶参与色素形成途径，多巴胺β羟化酶则与神经传导有关。细胞内铜离子浓度过低会影响这些酶的活性及相应的生理代谢途径，影响细胞的生存。但细胞内铜离子浓度超过生理需求也会引起严重的问题。铜离子能氧化蛋白，脂类和ＤＮＡ，同时促进形成自由基，引起细胞死亡［１］。人体很多疾病都是由于铜离子代谢异常引起的，其中最著名的就是Ｗｉｌｓｏｎ［２］ 和Ｍｅｎｋｓ［３］病，它们分别是由过多铜离子在细胞内堆积和细胞内铜离子浓度过低导致的。另外，铜离子缺乏还会引起心脏疾病［４］。所以，将细胞内铜离子浓度维持在一稳定水平对细胞生存至关重要。生理性铜离子浓度的维持主要在于四个环节：铜离子进入胞内（ｕｐｔａｋｅ）、胞内运送（ｔｒａｎｓｌｏｃａｔｉｏｎ）、合成金属蛋白（ｓｙｎｔｈｅｓｉｓ）及清除过多铜离子（ｅｌｉｍ ｉｎａｔｉｏｎ）［５］。对于过高或过低的铜离子浓度，细胞主要是通过改变流入量（ｉｎｆｌｕｘ）和流出量（ｅｆｆｌｕｘ）来应答。另外，金属硫蛋白可?

Copper is one of the most important trace elements for cell survival.There is a very complex and highly conserved system in cell to keep the copper concentration normal.\;In bacteria,there are three kinds of mechanism for copper tolerance:sequestration and sedimentation in Pseudomonas syringa ,P\|type ATPases in Enterococcus hirae and exclusion without P\|type ATPases in Escherichia coli. \;In yeast,copper is tightly related to iron metabolism.Copper,bound by Atxlp,will be transported into the Golgi Body by Ccc2p,which is a P\|type ATPase and highly homology to Cop A,Cop B,MND and WND.Then excessive copper will be excluded by Golgi Body.\;The mechanism of copper tolerance in human is very similar to that in yeast.The research in human concentrates on MND and WND ,which are the major pathogenic genes of Menks disease and Wilson disease respctively.They are also two P\|type ATPases and have all conserved motifs in P\|type ATPase.\;Though many genes in human copper tolerance system have been cloned,there are still mysteries in this process.Further research will help to elucidate this basic and important process.