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The (Bio)Chemistry of Non-Transferrin-Bound Iron

In healthy individuals, virtually all blood plasma iron is bound by transferrin. However, in several diseases and clinical conditions, hazardous non-transferrin-bound iron (NTBI) species occur. NTBI represents a potentially toxic iron form, being a direct cause of oxidative stress in the circulating...

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Autores principales: Silva, André M. N., Rangel, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951307/
https://www.ncbi.nlm.nih.gov/pubmed/35335148
http://dx.doi.org/10.3390/molecules27061784
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author Silva, André M. N.
Rangel, Maria
author_facet Silva, André M. N.
Rangel, Maria
author_sort Silva, André M. N.
collection PubMed
description In healthy individuals, virtually all blood plasma iron is bound by transferrin. However, in several diseases and clinical conditions, hazardous non-transferrin-bound iron (NTBI) species occur. NTBI represents a potentially toxic iron form, being a direct cause of oxidative stress in the circulating compartment and tissue iron loading. The accumulation of these species can cause cellular damage in several organs, namely, the liver, spleen, and heart. Despite its pathophysiological relevance, the chemical nature of NTBI remains elusive. This has precluded its use as a clinical biochemical marker and the development of targeted therapies. Herein, we make a critical assessment of the current knowledge of NTBI speciation. The currently accepted hypotheses suggest that NTBI is mostly iron bound to citric acid and iron bound to serum albumin, but the chemistry of this system remains fuzzy. We explore the complex chemistry of iron complexation by citric acid and its implications towards NTBI reactivity. Further, the ability of albumin to bind iron is revised and the role of protein post-translational modifications on iron binding is discussed. The characterization of the NTBI species structure may be the starting point for the development of a standardized analytical assay, the better understanding of these species’ reactivity or the identification of NTBI uptake mechanisms by different cell types, and finally, to the development of new therapies.
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spelling pubmed-89513072022-03-26 The (Bio)Chemistry of Non-Transferrin-Bound Iron Silva, André M. N. Rangel, Maria Molecules Review In healthy individuals, virtually all blood plasma iron is bound by transferrin. However, in several diseases and clinical conditions, hazardous non-transferrin-bound iron (NTBI) species occur. NTBI represents a potentially toxic iron form, being a direct cause of oxidative stress in the circulating compartment and tissue iron loading. The accumulation of these species can cause cellular damage in several organs, namely, the liver, spleen, and heart. Despite its pathophysiological relevance, the chemical nature of NTBI remains elusive. This has precluded its use as a clinical biochemical marker and the development of targeted therapies. Herein, we make a critical assessment of the current knowledge of NTBI speciation. The currently accepted hypotheses suggest that NTBI is mostly iron bound to citric acid and iron bound to serum albumin, but the chemistry of this system remains fuzzy. We explore the complex chemistry of iron complexation by citric acid and its implications towards NTBI reactivity. Further, the ability of albumin to bind iron is revised and the role of protein post-translational modifications on iron binding is discussed. The characterization of the NTBI species structure may be the starting point for the development of a standardized analytical assay, the better understanding of these species’ reactivity or the identification of NTBI uptake mechanisms by different cell types, and finally, to the development of new therapies. MDPI 2022-03-09 /pmc/articles/PMC8951307/ /pubmed/35335148 http://dx.doi.org/10.3390/molecules27061784 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
Silva, André M. N.
Rangel, Maria
The (Bio)Chemistry of Non-Transferrin-Bound Iron
title The (Bio)Chemistry of Non-Transferrin-Bound Iron
title_full The (Bio)Chemistry of Non-Transferrin-Bound Iron
title_fullStr The (Bio)Chemistry of Non-Transferrin-Bound Iron
title_full_unstemmed The (Bio)Chemistry of Non-Transferrin-Bound Iron
title_short The (Bio)Chemistry of Non-Transferrin-Bound Iron
title_sort (bio)chemistry of non-transferrin-bound iron
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8951307/
https://www.ncbi.nlm.nih.gov/pubmed/35335148
http://dx.doi.org/10.3390/molecules27061784
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