The biology of mammalian multi-copper ferroxidases
| Autor: | Sheridan L. Helman, Jie Zhou, Brie K. Fuqua, Yan Lu, James F. Collins, Huijun Chen, Christopher D. Vulpe, Gregory J. Anderson, David M. Frazer |
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| Rok vydání: | 2023 |
| Předmět: |
Biochemistry & Molecular Biology
Knockout Iron 1.1 Normal biological development and functioning General Biochemistry Genetics and Molecular Biology Article Ferroxidase Biomaterials Mice Underpinning research Animals 2.1 Biological and endogenous factors Aetiology Biology Nutrition Mammals Metals and Alloys Ceruloplasmin Hephaestin Zyklopen Generic health relevance Biochemistry and Cell Biology General Agricultural and Biological Sciences Digestive Diseases Oxidation-Reduction Copper |
| Zdroj: | Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine, vol 36, iss 2 Biometals |
| Popis: | The mammalian multicopper ferroxidases (MCFs) ceruloplasmin (CP), hephaestin (HEPH) and zyklopen (ZP) comprise a family of conserved enzymes that are essential for body iron homeostasis. Each of these enzymes contains six biosynthetically incorporated copper atoms which act as intermediate electron acceptors, and the oxidation of iron is associated with the four electron reduction of dioxygen to generate two water molecules. CP occurs in both a secreted and GPI-linked (membrane-bound) form, while HEPH and ZP each contain a single C-terminal transmembrane domain. These enzymes function to ensure the efficient oxidation of iron so that it can be effectively released from tissues via the iron export protein ferroportin and subsequently bound to the iron carrier protein transferrin in the blood. CP is particularly important in facilitating iron release from the liver and central nervous system, HEPH is the major MCF in the small intestine and is critical for dietary iron absorption, and ZP is important for normal hair development. CP and HEPH (and possibly ZP) function in multiple tissues. These proteins also play other (non-iron-related) physiological roles, but many of these are ill-defined. In addition to disrupting iron homeostasis, MCF dysfunction perturbs neurological and immune function, alters cancer susceptibility, and causes hair loss, but, despite their importance, how MCFs co-ordinately maintain body iron homeostasis and perform other functions remains incompletely understood. |
| Databáze: | OpenAIRE |
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