Cargando…

Ferric pyrophosphate citrate: interactions with transferrin

There are several options available for intravenous application of iron supplements, but they all have a similar structure:—an iron core surrounded by a carbohydrate coating. These nanoparticles require processing by the reticuloendothelial system to release iron, which is subsequently picked up by...

Descripción completa

Detalles Bibliográficos
Autores principales: Pratt, Raymond, Handelman, Garry J., Edwards, Thomas E., Gupta, Ajay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245029/
https://www.ncbi.nlm.nih.gov/pubmed/30311019
http://dx.doi.org/10.1007/s10534-018-0142-2
_version_ 1783372164269867008
author Pratt, Raymond
Handelman, Garry J.
Edwards, Thomas E.
Gupta, Ajay
author_facet Pratt, Raymond
Handelman, Garry J.
Edwards, Thomas E.
Gupta, Ajay
author_sort Pratt, Raymond
collection PubMed
description There are several options available for intravenous application of iron supplements, but they all have a similar structure:—an iron core surrounded by a carbohydrate coating. These nanoparticles require processing by the reticuloendothelial system to release iron, which is subsequently picked up by the iron-binding protein transferrin and distributed throughout the body, with most of the iron supplied to the bone marrow. This process risks exposing cells and tissues to free iron, which is potentially toxic due to its high redox activity. A new parenteral iron formation, ferric pyrophosphate citrate (FPC), has a novel structure that differs from conventional intravenous iron formulations, consisting of an iron atom complexed to one pyrophosphate and two citrate anions. In this study, we show that FPC can directly transfer iron to apo-transferrin. Kinetic analyses reveal that FPC donates iron to apo-transferrin with fast binding kinetics. In addition, the crystal structure of transferrin bound to FPC shows that FPC can donate iron to both iron-binding sites found within the transferrin structure. Examination of the iron-binding sites demonstrates that the iron atoms in both sites are fully encapsulated, forming bonds with amino acid side chains in the protein as well as pyrophosphate and carbonate anions. Taken together, these data demonstrate that, unlike intravenous iron formulations, FPC can directly and rapidly donate iron to transferrin in a manner that does not expose cells and tissues to the damaging effects of free, redox-active iron.
format Online
Article
Text
id pubmed-6245029
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Springer Netherlands
record_format MEDLINE/PubMed
spelling pubmed-62450292018-12-04 Ferric pyrophosphate citrate: interactions with transferrin Pratt, Raymond Handelman, Garry J. Edwards, Thomas E. Gupta, Ajay Biometals Article There are several options available for intravenous application of iron supplements, but they all have a similar structure:—an iron core surrounded by a carbohydrate coating. These nanoparticles require processing by the reticuloendothelial system to release iron, which is subsequently picked up by the iron-binding protein transferrin and distributed throughout the body, with most of the iron supplied to the bone marrow. This process risks exposing cells and tissues to free iron, which is potentially toxic due to its high redox activity. A new parenteral iron formation, ferric pyrophosphate citrate (FPC), has a novel structure that differs from conventional intravenous iron formulations, consisting of an iron atom complexed to one pyrophosphate and two citrate anions. In this study, we show that FPC can directly transfer iron to apo-transferrin. Kinetic analyses reveal that FPC donates iron to apo-transferrin with fast binding kinetics. In addition, the crystal structure of transferrin bound to FPC shows that FPC can donate iron to both iron-binding sites found within the transferrin structure. Examination of the iron-binding sites demonstrates that the iron atoms in both sites are fully encapsulated, forming bonds with amino acid side chains in the protein as well as pyrophosphate and carbonate anions. Taken together, these data demonstrate that, unlike intravenous iron formulations, FPC can directly and rapidly donate iron to transferrin in a manner that does not expose cells and tissues to the damaging effects of free, redox-active iron. Springer Netherlands 2018-10-11 2018 /pmc/articles/PMC6245029/ /pubmed/30311019 http://dx.doi.org/10.1007/s10534-018-0142-2 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Pratt, Raymond
Handelman, Garry J.
Edwards, Thomas E.
Gupta, Ajay
Ferric pyrophosphate citrate: interactions with transferrin
title Ferric pyrophosphate citrate: interactions with transferrin
title_full Ferric pyrophosphate citrate: interactions with transferrin
title_fullStr Ferric pyrophosphate citrate: interactions with transferrin
title_full_unstemmed Ferric pyrophosphate citrate: interactions with transferrin
title_short Ferric pyrophosphate citrate: interactions with transferrin
title_sort ferric pyrophosphate citrate: interactions with transferrin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245029/
https://www.ncbi.nlm.nih.gov/pubmed/30311019
http://dx.doi.org/10.1007/s10534-018-0142-2
work_keys_str_mv AT prattraymond ferricpyrophosphatecitrateinteractionswithtransferrin
AT handelmangarryj ferricpyrophosphatecitrateinteractionswithtransferrin
AT edwardsthomase ferricpyrophosphatecitrateinteractionswithtransferrin
AT guptaajay ferricpyrophosphatecitrateinteractionswithtransferrin