Department of Medical Laboratory Diagnosis, University Hospital Center Split, Split, Croatia.
Biochem Med (Zagreb). 2012;22(3):311-28. doi: 10.11613/bm.2012.034.
Iron metabolism has been intensively examined over the last decade and there are many new players in this field which are worth to be introduced. Since its discovery many studies confirmed role of liver hormone hepcidin as key regulator of iron metabolism and pointed out liver as the central organ of system iron homeostasis. Liver cells receive multiple signals related to iron balance and respond by transcriptional regulation of hepcidin expression. This liver hormone is negative regulator of iron metabolism that represses iron efflux from macrophages, hepatocytes and enterocytes by its binding to iron export protein ferroportin. Ferroportin degradation leads to cellular iron retention and decreased iron availability. At level of a cell IRE/IRP (iron responsive elements/iron responsive proteins) system allows tight regulation of iron assimilation that prevents an excess of free intracellular iron which could lead to oxidative stress and damage of DNA, proteins and lipid membranes by ROS (reactive oxygen species). At the same time IRE/IRP system provides sufficient iron in order to meet the metabolic needs. Recently a significant progress in understanding of iron metabolism has been made and new molecular participants have been characterized. Article gives an overview of the current understanding of iron metabolism: absorption, distribution, cellular uptake, release, and storage. We also discuss mechanisms underlying systemic and cellular iron regulation with emphasis on central regulatory hormone hepcidin.
过去十年中，人们对铁代谢进行了深入研究，该领域出现了许多值得介绍的新角色。自发现以来，许多研究证实了肝脏激素铁调素作为铁代谢关键调节剂的作用，并指出肝脏是系统铁稳态的中心器官。肝细胞接收与铁平衡相关的多种信号，并通过铁调素表达的转录调控做出反应。这种肝脏激素是铁代谢的负调节剂，通过与铁输出蛋白铁蛋白结合，抑制巨噬细胞、肝细胞和肠细胞中铁的流出。铁蛋白降解导致细胞内铁的保留和铁的可用性降低。在细胞水平，IRE/IRP（铁反应元件/铁反应蛋白）系统允许对铁吸收进行严格调节，防止过多的游离细胞内铁导致氧化应激和 DNA、蛋白质和脂质膜的损伤由 ROS（活性氧）引起。同时，IRE/IRP 系统提供足够的铁以满足代谢需求。最近，人们对铁代谢的理解取得了重大进展，并对新的分子参与者进行了描述。本文概述了目前对铁代谢的理解：吸收、分布、细胞摄取、释放和储存。我们还讨论了系统和细胞铁调节的机制，重点是中枢调节激素铁调素。
