Maret Wolfgang
Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King's College London, London, United Kingdom.
J Nutr. 2025 Mar;155(3):669-675. doi: 10.1016/j.tjnut.2025.01.004. Epub 2025 Jan 8.
This perspective discusses the essential micronutrient zinc, which functions in >3000 human proteins (the zinc proteome), and the implications of three aspects to ascertain an adequate zinc status for human health. First, the advent of highly sensitive fluorescent (bio)chemicals revealed cellular pools of zinc ions involved in signaling and secretion from cells for paracrine, autocrine, and possibly endocrine functions. Zinc signaling adds a yet unaccounted number of targeted proteins to the already impressive number of zinc proteins. Second, cellular zinc concentrations are remarkably high in the order of the concentrations of major metabolites and, therefore, at the cellular level zinc is not a trace element. Zinc is also not an antioxidant because zinc ions are redox-inactive in biology. However, zinc can express indirect pro-oxidant or proantioxidant effects depending on how cellular zinc is buffered. Zinc sites in proteins and other biomolecules can become redox-active when zinc is bound to the redox-active sulfur donor atom of cysteine. This interaction links zinc and redox metabolism, confers mobility on tightly bound zinc, and has implications for treating zinc deficiency. Third, the concept of zinc deficiency in blood as the only measure of an inadequate zinc status needs to be extended to zinc dyshomeostasis in cells because overwhelming the mechanisms controlling cellular zinc homeostasis can result in either not enough or too much available zinc. We need additional biomarkers of zinc status that determine cell-specific changes and perturbations of the system regulating cellular zinc, including functional deficits, and address the multiple genetic and environmental factors that can cause a conditioned zinc deficiency or overload. Considering the wider context of altered zinc availability in different organs, cells, and organelles impinges on whether zinc supplementation will be efficacious and adds another dimension to the already high health burden of zinc deficiency and its sequelae worldwide.
本文观点探讨了必需的微量营养素锌，它在3000多种人类蛋白质（锌蛋白质组）中发挥作用，以及确定人体健康所需锌充足状态的三个方面的影响。首先，高灵敏度荧光（生物）化学物质的出现揭示了参与细胞信号传导和分泌以实现旁分泌、自分泌以及可能的内分泌功能的锌离子细胞池。锌信号传导在已数量可观的锌蛋白基础上又增加了尚未统计的靶向蛋白数量。其次，细胞内锌的浓度与主要代谢物的浓度处于同一数量级，非常高，因此在细胞水平上锌不是微量元素。锌也不是抗氧化剂，因为锌离子在生物学中没有氧化还原活性。然而，锌可根据细胞内锌的缓冲方式表现出间接的促氧化或抗氧化作用。当锌与半胱氨酸的氧化还原活性硫供体原子结合时，蛋白质和其他生物分子中的锌位点可变得具有氧化还原活性。这种相互作用将锌与氧化还原代谢联系起来，赋予紧密结合的锌流动性，并对治疗锌缺乏症有影响。第三，将血液中锌缺乏作为锌状态不足的唯一衡量标准的概念需要扩展到细胞内锌稳态失衡，因为控制细胞锌稳态的机制不堪重负可能导致可用锌不足或过多。我们需要额外的锌状态生物标志物，以确定调节细胞锌的系统的细胞特异性变化和扰动，包括功能缺陷，并解决可能导致条件性锌缺乏或过载的多种遗传和环境因素。考虑到不同器官、细胞和细胞器中锌可用性改变的更广泛背景，这会影响锌补充剂是否有效，并为全球范围内已经很高的锌缺乏及其后遗症的健康负担又增加了一个层面。
