Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Biochemistry and Molecular Biophysics Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Curr Biol. 2021 May 10;31(9):R421-R427. doi: 10.1016/j.cub.2021.03.054.
Metals are vital for life as they are necessary for essential biological processes. Traditionally, metals are categorized as either dynamic signals or static cofactors. Redox-inactive metals such as calcium (Ca), potassium (K), sodium (Na), and zinc (Zn) signal through large fluctuations in their metal-ion pools. In contrast, redox-active transition metals such as copper (Cu) and iron (Fe) drive catalysis and are largely characterized as static cofactors that must be buried and protected within the active sites of proteins, due to their ability to generate damaging reactive-oxygen species through Fenton chemistry. Cu has largely been studied as a static cofactor in fundamental processes from cellular respiration to pigmentation, working through cytochrome c oxidase and tyrosinase, respectively. However, within the last decade, a new paradigm in nutrient sensing and protein regulation - termed 'metalloallostery' - has emerged, expanding the repertoire of Cu beyond the catalytic proteins to dynamic signaling molecules essential for cellular processes that impact normal physiology and disease states. In this Primer we introduce both the 'traditional' and emerging roles for Cu in biology and the many ways in which Cu intersects with human health.
金属对于生命至关重要，因为它们是许多基本生物过程所必需的。传统上，金属被分为动态信号或静态辅因子。像钙（Ca）、钾（K）、钠（Na）和锌（Zn）这样的氧化还原非活性金属通过其金属离子池的大幅波动来传递信号。相比之下，氧化还原活性的过渡金属，如铜（Cu）和铁（Fe），则通过芬顿化学产生具有破坏性的活性氧物种，因此主要被认为是静态辅因子，必须被埋藏和保护在蛋白质的活性部位。Cu 主要作为细胞呼吸到色素沉着等基本过程中的静态辅因子进行研究，分别通过细胞色素 c 氧化酶和酪氨酸酶发挥作用。然而，在过去十年中，一种新的营养感应和蛋白质调节模式——“金属变构作用”出现了，这将 Cu 的作用范围从催化蛋白扩展到了动态信号分子，这些信号分子对于影响正常生理和疾病状态的细胞过程至关重要。在这篇简介中，我们介绍了 Cu 在生物学中的“传统”和新兴作用，以及 Cu 与人类健康的许多交集。
