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Iron Metabolism in the Disorders of Heme Biosynthesis

Given its remarkable property to easily switch between different oxidative states, iron is essential in countless cellular functions which involve redox reactions. At the same time, uncontrolled interactions between iron and its surrounding milieu may be damaging to cells and tissues. Heme—the iron-...

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Autores principales: Ricci, Andrea, Di Betto, Giada, Bergamini, Elisa, Buzzetti, Elena, Corradini, Elena, Ventura, Paolo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9505951/
https://www.ncbi.nlm.nih.gov/pubmed/36144223
http://dx.doi.org/10.3390/metabo12090819
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author Ricci, Andrea
Di Betto, Giada
Bergamini, Elisa
Buzzetti, Elena
Corradini, Elena
Ventura, Paolo
author_facet Ricci, Andrea
Di Betto, Giada
Bergamini, Elisa
Buzzetti, Elena
Corradini, Elena
Ventura, Paolo
author_sort Ricci, Andrea
collection PubMed
description Given its remarkable property to easily switch between different oxidative states, iron is essential in countless cellular functions which involve redox reactions. At the same time, uncontrolled interactions between iron and its surrounding milieu may be damaging to cells and tissues. Heme—the iron-chelated form of protoporphyrin IX—is a macrocyclic tetrapyrrole and a coordination complex for diatomic gases, accurately engineered by evolution to exploit the catalytic, oxygen-binding, and oxidoreductive properties of iron while minimizing its damaging effects on tissues. The majority of the body production of heme is ultimately incorporated into hemoglobin within mature erythrocytes; thus, regulation of heme biosynthesis by iron is central in erythropoiesis. Additionally, heme is a cofactor in several metabolic pathways, which can be modulated by iron-dependent signals as well. Impairment in some steps of the pathway of heme biosynthesis is the main pathogenetic mechanism of two groups of diseases collectively known as porphyrias and congenital sideroblastic anemias. In porphyrias, according to the specific enzyme involved, heme precursors accumulate up to the enzyme stop in disease-specific patterns and organs. Therefore, different porphyrias manifest themselves under strikingly different clinical pictures. In congenital sideroblastic anemias, instead, an altered utilization of mitochondrial iron by erythroid precursors leads to mitochondrial iron overload and an accumulation of ring sideroblasts in the bone marrow. In line with the complexity of the processes involved, the role of iron in these conditions is then multifarious. This review aims to summarise the most important lines of evidence concerning the interplay between iron and heme metabolism, as well as the clinical and experimental aspects of the role of iron in inherited conditions of altered heme biosynthesis.
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spelling pubmed-95059512022-09-24 Iron Metabolism in the Disorders of Heme Biosynthesis Ricci, Andrea Di Betto, Giada Bergamini, Elisa Buzzetti, Elena Corradini, Elena Ventura, Paolo Metabolites Review Given its remarkable property to easily switch between different oxidative states, iron is essential in countless cellular functions which involve redox reactions. At the same time, uncontrolled interactions between iron and its surrounding milieu may be damaging to cells and tissues. Heme—the iron-chelated form of protoporphyrin IX—is a macrocyclic tetrapyrrole and a coordination complex for diatomic gases, accurately engineered by evolution to exploit the catalytic, oxygen-binding, and oxidoreductive properties of iron while minimizing its damaging effects on tissues. The majority of the body production of heme is ultimately incorporated into hemoglobin within mature erythrocytes; thus, regulation of heme biosynthesis by iron is central in erythropoiesis. Additionally, heme is a cofactor in several metabolic pathways, which can be modulated by iron-dependent signals as well. Impairment in some steps of the pathway of heme biosynthesis is the main pathogenetic mechanism of two groups of diseases collectively known as porphyrias and congenital sideroblastic anemias. In porphyrias, according to the specific enzyme involved, heme precursors accumulate up to the enzyme stop in disease-specific patterns and organs. Therefore, different porphyrias manifest themselves under strikingly different clinical pictures. In congenital sideroblastic anemias, instead, an altered utilization of mitochondrial iron by erythroid precursors leads to mitochondrial iron overload and an accumulation of ring sideroblasts in the bone marrow. In line with the complexity of the processes involved, the role of iron in these conditions is then multifarious. This review aims to summarise the most important lines of evidence concerning the interplay between iron and heme metabolism, as well as the clinical and experimental aspects of the role of iron in inherited conditions of altered heme biosynthesis. MDPI 2022-08-31 /pmc/articles/PMC9505951/ /pubmed/36144223 http://dx.doi.org/10.3390/metabo12090819 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Ricci, Andrea
Di Betto, Giada
Bergamini, Elisa
Buzzetti, Elena
Corradini, Elena
Ventura, Paolo
Iron Metabolism in the Disorders of Heme Biosynthesis
title Iron Metabolism in the Disorders of Heme Biosynthesis
title_full Iron Metabolism in the Disorders of Heme Biosynthesis
title_fullStr Iron Metabolism in the Disorders of Heme Biosynthesis
title_full_unstemmed Iron Metabolism in the Disorders of Heme Biosynthesis
title_short Iron Metabolism in the Disorders of Heme Biosynthesis
title_sort iron metabolism in the disorders of heme biosynthesis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9505951/
https://www.ncbi.nlm.nih.gov/pubmed/36144223
http://dx.doi.org/10.3390/metabo12090819
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