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, uncon- trolled 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 coordina- tion 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 por- phyrias manifest themselves under strikingly different clinical pictures. In congenital sideroblastic anemias, instead, an altered utilization of mitochondrial iron by erythroid precursors leads to mito- chondrial 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 be- tween iron and heme metabolism, as well as the clinical and experimental aspects of the role of iron in inherited conditions of altered heme biosynthesis.

Iron Metabolism in the Disorders of Heme Biosynthesis / Ricci, Andrea; Di Betto, Giada; Bergamini, Elisa; Buzzetti, Elena; Corradini, Elena; Ventura, Paolo. - In: METABOLITES. - ISSN 2218-1989. - 12:(2022), pp. 819-848. [10.3390/metabo12090819]

Iron Metabolism in the Disorders of Heme Biosynthesis

Andrea Ricci
Writing – Original Draft Preparation
;
Giada Di Betto
Writing – Original Draft Preparation
;
Elisa Bergamini
Writing – Original Draft Preparation
;
Elena Buzzetti
Writing – Original Draft Preparation
;
Elena Corradini
Writing – Review & Editing
;
Paolo Ventura
Writing – Original Draft Preparation
2022

Abstract

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, uncon- trolled 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 coordina- tion 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 por- phyrias manifest themselves under strikingly different clinical pictures. In congenital sideroblastic anemias, instead, an altered utilization of mitochondrial iron by erythroid precursors leads to mito- chondrial 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 be- tween iron and heme metabolism, as well as the clinical and experimental aspects of the role of iron in inherited conditions of altered heme biosynthesis.
31-ago-2022
12
819
848
Iron Metabolism in the Disorders of Heme Biosynthesis / Ricci, Andrea; Di Betto, Giada; Bergamini, Elisa; Buzzetti, Elena; Corradini, Elena; Ventura, Paolo. - In: METABOLITES. - ISSN 2218-1989. - 12:(2022), pp. 819-848. [10.3390/metabo12090819]
Ricci, Andrea; Di Betto, Giada; Bergamini, Elisa; Buzzetti, Elena; Corradini, Elena; Ventura, Paolo
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1286528
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