Intracellular copper transport in mammals
Intracellular copper transport in mammals
复制标题
DOI：
10.1093/jn/134.5.1003
复制
发表时间：
2004-05-01
影响因子：
4.2
通讯作者：
Gybina, AA
中科院分区：
文献类型：
--
作者：
Prohaska, JR;Gybina, AA
铜是大约十几种铜酶的必需辅助因子，其中铜与活性位点的特定氨基酸残基结合。然而，游离亚铜离子很容易与过氧化氢反应，产生有害的羟基自由基。因此，铜的稳态受到非常严格的调节，未结合的铜浓度极低。由质膜转运蛋白 Ctr1 输入的铜快速与细胞内铜伴侣蛋白结合。 Atox1 将铜输送到分泌途径，并与肝脏中的铜转运 ATP 酶 ATP7B 或其他细胞中的 ATP7A 对接。 ATP7B 与新发现的伴侣 Murr1（犬铜中毒中缺失的蛋白质）协同作用，将铜引导至血浆铜蓝蛋白或胆汁排泄。 ATP7A 将转高尔基体网络内的铜引导至蛋白质多巴胺 β-单加氧酶、肽酰甘氨酸 α-酰胺化单加氧酶、赖氨酰氧化酶和酪氨酸酶，具体取决于细胞类型。 CCS 是 Cu,Zn-超氧化物歧化酶的铜伴侣；它在细胞质和线粒体间隙中输送铜。 Cox17 通过伴侣 Cox11、Sco1 和 Sco2 将铜递送至线粒体至细胞色素 c 氧化酶。可能存在其他铜伴侣，可能包括金属硫蛋白和淀粉样前体蛋白 (APP)。遗传和营养研究已经阐明了这些铜结合蛋白的本质。它们水平的改变与严重的病理有关。
Copper is an essential cofactor for approximately a dozen cuproenzymes in which copper is bound to specific amino acid residues in an active site. However, free cuprous ions react readily with hydrogen peroxide to yield the deleterious hydroxyl radical. Therefore, copper homeostasis is regulated very tightly, and unbound copper is extremely low in concentration. Copper imported by the plasma membrane transport protein Ctr1 rapidly binds to intracellular copper chaperone proteins. Atox1 delivers copper to the secretory pathway and docks with either copper-transporting ATPase ATP7B in the liver or ATP7A in other cells. ATP7B directs copper to plasma ceruloplasmin or to biliary excretion in concert with a newly discovered chaperone, Murr1, the protein missing in canine copper toxicosis. ATP7A directs copper within the transgolgi network to the proteins dopamine beta-monooxgenase, peptidylglycine alpha-amidating monooxygenase, lysyl oxidase, and tyrosinase, depending on the cell type. CCS is the copper chaperone for Cu,Zn-superoxide dismutase; it delivers copper in the cytoplasm and intermitochondrial space. Cox17 delivers copper to mitochondria to cytochrome c oxidase via the chaperones Cox11, Sco1, and Sco2. Other copper chaperones may exist and might include metallothionein and amyloid precursor protein (APP). Genetic and nutritional studies have illustrated the essential nature of these copper-binding proteins; alterations in their levels are associated with severe pathology.