Suzuki M, Gitlin J D
Second Department of Pediatrics, Toho University School of Medicine, Tokyo, Japan.
Pediatr Int. 1999 Aug;41(4):436-42. doi: 10.1046/j.1442-200x.1999.01090.x.
Copper is a heavy metal ion essential for the activity of a variety of enzymes in the body. In excess, copper is a very toxic ion and therefore efficient regulation of its metabolism is required. This is dramatically illustrated by the genetic disorders X-linked Menkes disease and autosomal recessive Wilson's disease. In 1993, both the Menkes and Wilson's genes were isolated and it was found that these genes encode homologous cation copper transporting P-type ATPase proteins. The Menkes protein (ATP7A) is expressed in most tissues, except liver. In contrast, the Wilson's protein (ATP7B) is abundantly expressed in liver. Intracellular localization of those proteins was investigated. Both ATP7A and ATP7B are localized in the trans-Golgi network and post-Golgi vesicular compartment (PGVC) in the cell. This intracellular localization was altered by the copper content present in the cell. This result may support the hypothesis that ATP7A and ATP7B are involved in cellular copper transport and those proteins could be suitable models for elucidating intracellular copper metabolism.
铜是一种重金属离子，对人体多种酶的活性至关重要。过量的铜是一种剧毒离子，因此需要对其代谢进行有效调节。X连锁的门克斯病和常染色体隐性威尔逊病这两种遗传疾病就显著地说明了这一点。1993年，门克斯病基因和威尔逊病基因均被分离出来，发现这些基因编码同源的阳离子铜转运P型ATP酶蛋白。门克斯蛋白（ATP7A）在除肝脏外的大多数组织中表达。相比之下，威尔逊蛋白（ATP7B）在肝脏中大量表达。对这些蛋白的细胞内定位进行了研究。ATP7A和ATP7B均定位于细胞中的反式高尔基体网络和高尔基体后囊泡区室（PGVC）。这种细胞内定位会因细胞中铜的含量而改变。这一结果可能支持以下假说：ATP7A和ATP7B参与细胞铜转运，并且这些蛋白可能是阐明细胞内铜代谢的合适模型。
