Hill G M, Link J E
Animal Science Department, Michigan State University, East Lansing, MI 48824, USA.
J Anim Sci. 2009 Apr;87(14 Suppl):E85-9. doi: 10.2527/jas.2008-1341. Epub 2008 Sep 26.
Before the discovery and elucidation of transporters, mammals were thought to cotransport Cu or Zn as an anionic complex, such as binding with an AA as a chelate or a receptor such as transferrin. In 1995, the first mammalian Zn transporter (ZnT) gene, ZnT1, was identified. However, 2 protein families are now thought to be involved in Zn transport. The ZnT family reduces intracellular Zn by aiding in efflux from the cell or promoting the influx into intracellular vesicles. The mechanism of ZnT transport against a Zn concentration gradient is unknown; however, only ZnT1 appears to be located at the plasma membrane. It has been shown to respond in tissues in a variety of ways to Zn reduction and supplementation. In our laboratory, we have found ZnT1 and metallothionein to work in concert during pharmacological Zn supplementation. The second protein family, Zip proteins, provides Zn transport from extracellular fluid or intracellular vesicles into the cytoplasm and has not been identified in a livestock species. Like Zn, no good indicator of status has been identified for Cu. However, the recent identification of Cu transporters and chaperones gives researchers the opportunity to understand the regulation of Cu trafficking where the proteins are modified by posttranslational mechanisms. Two Cu transporters, Ctr1 and Ctr3, mediate high-affinity Cu uptake. A small cytoplasmic protein, MURR1, has been identified in human hepatic tissue, but its role in Cu metabolism is unknown. The discovery of Cu chaperones that are involved in facilitating Cu absorption into proteins may provide an excellent status indicator. It has been shown that the Cu chaperone for Cu/Zn superoxide dismutase (CCS) is increased in tissue of Cu-deficient rats, induced when moderately high Zn diets are fed. We have recently found CCS in the young pig. Other Cu chaperone proteins that have been identified are COX17 and Atox1. As with CCS, they are involved in making Cu available to apo-enzymes inside the cell. It is essential that these new molecular findings be used to evaluate the bioavailability of and nutritional need for Cu and Zn in livestock.
在转运体被发现和阐明之前，哺乳动物被认为是以阴离子复合物的形式共转运铜或锌，例如与氨基酸结合形成螯合物，或与转铁蛋白等受体结合。1995年，第一个哺乳动物锌转运体（ZnT）基因ZnT1被鉴定出来。然而，现在认为有两个蛋白质家族参与锌的转运。ZnT家族通过协助锌从细胞外流或促进锌流入细胞内囊泡来降低细胞内锌的含量。ZnT逆锌浓度梯度转运的机制尚不清楚；然而，只有ZnT1似乎位于质膜上。已经表明，它在各种组织中对锌的减少和补充有不同的反应。在我们实验室，我们发现ZnT1和金属硫蛋白在药理学补锌过程中协同作用。第二个蛋白质家族，即Zip蛋白，负责将锌从细胞外液或细胞内囊泡转运到细胞质中，目前尚未在牲畜物种中鉴定出来。与锌一样，尚未确定铜状态的良好指标。然而，最近铜转运体和伴侣蛋白的鉴定为研究人员提供了了解铜运输调控的机会，在这种调控中，蛋白质通过翻译后机制进行修饰。两种铜转运体Ctr1和Ctr3介导高亲和力的铜摄取。一种小的细胞质蛋白MURR1已在人类肝脏组织中被鉴定出来，但其在铜代谢中的作用尚不清楚。参与促进铜吸收到蛋白质中的铜伴侣蛋白的发现可能提供一个良好的状态指标。已经表明，铜/锌超氧化物歧化酶（CCS）的铜伴侣蛋白在缺铜大鼠的组织中增加，在饲喂中等高锌日粮时被诱导产生。我们最近在幼猪中发现了CCS。已鉴定出的其他铜伴侣蛋白是COX17和Atox1。与CCS一样，它们参与使铜可用于细胞内的脱辅基酶。必须利用这些新的分子发现来评估牲畜中铜和锌的生物利用率及营养需求。
