Vulpe C D, Packman S
Department of Biochemistry and Biophysics, University of California, San Francisco 94143-0748, USA.
Annu Rev Nutr. 1995;15:293-322. doi: 10.1146/annurev.nu.15.070195.001453.
Cellular copper transport processes are required by all organisms for correct utilization in cell biochemical processes and avoidance of the toxicity of copper excess. Copper import into bacterial, yeast, and mammalian cells requires the coordinate function of proteins with both metal-binding and catalytic domains in mediated transport steps. Following entry, detoxification mechanisms found across species include the binding of copper to specific proteins (e.g. metallothioneins) and the transfer of copper into isolated cell compartments (e.g. periplasmic space, lysosome). Multiple proteins mediate intracellular transfers in bacteria, and glutathione may play a major role in cytosolic copper delivery to cuproenzymes in mammalian cells. Study of two human disorders of copper transport, Menkes disease and Wilson disease, led to the identification of an important category of proteins mediating cell copper export. The Menkes and Wilson disease gene products are copper-transporting ATPases of the P type, with ATPase domains and N-terminal metal-binding amino acid motifs that are evolutionarily conserved in unicellular and mammalian organisms. These observations suggest that yeast and bacterial copper transport proteins, or individual domains of these proteins, may generally have homologues in mammalian systems.
所有生物体都需要细胞铜转运过程，以便在细胞生化过程中正确利用铜，并避免铜过量产生的毒性。细菌、酵母和哺乳动物细胞摄取铜需要在介导的转运步骤中，具有金属结合和催化结构域的蛋白质协同发挥作用。铜进入细胞后，跨物种发现的解毒机制包括铜与特定蛋白质（如金属硫蛋白）结合，以及将铜转移到隔离的细胞区室（如周质空间、溶酶体）。多种蛋白质介导细菌细胞内的铜转运，而谷胱甘肽可能在将胞质铜递送至哺乳动物细胞中的铜酶过程中起主要作用。对两种人类铜转运障碍疾病——门克斯病和威尔逊病的研究，促成了一类介导细胞铜输出的重要蛋白质的发现。门克斯病和威尔逊病的基因产物是P型铜转运ATP酶，并具有ATP酶结构域和N端金属结合氨基酸基序，这些在单细胞生物和哺乳动物中具有进化保守性。这些观察结果表明，酵母和细菌的铜转运蛋白或这些蛋白质的单个结构域，在哺乳动物系统中通常可能具有同源物。
