Cargando…

Vitamin D Binding Protein: A Historic Overview

Vitamin D and all its metabolites are bound to a specific vitamin D binding protein, DBP. This protein was originally first discovered by its worldwide polymorphism and called Group-specific Component (GC). We now know that DBP and GC are the same protein and appeared early in the evolution of verte...

Descripción completa

Detalles Bibliográficos
Autores principales: Bouillon, Roger, Schuit, Frans, Antonio, Leen, Rastinejad, Fraydoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965021/
https://www.ncbi.nlm.nih.gov/pubmed/31998239
http://dx.doi.org/10.3389/fendo.2019.00910
_version_ 1783488570238959616
author Bouillon, Roger
Schuit, Frans
Antonio, Leen
Rastinejad, Fraydoon
author_facet Bouillon, Roger
Schuit, Frans
Antonio, Leen
Rastinejad, Fraydoon
author_sort Bouillon, Roger
collection PubMed
description Vitamin D and all its metabolites are bound to a specific vitamin D binding protein, DBP. This protein was originally first discovered by its worldwide polymorphism and called Group-specific Component (GC). We now know that DBP and GC are the same protein and appeared early in the evolution of vertebrates. DBP is genetically the oldest member of the albuminoid family (including albumin, α-fetoprotein and afamin, all involved in transport of fatty acids or hormones). DBP has a single binding site for all vitamin D metabolites and has a high affinity for 25OHD and 1,25(OH)2D, thereby creating a large pool of circulating 25OHD, which prevents rapid vitamin D deficiency. DBP of higher vertebrates (not amphibians or reptiles) binds with very high affinity actin, thereby preventing the formation of polymeric actin fibrils in the circulation after tissue damage. Megalin is a cargo receptor and is together with cubilin needed to reabsorb DBP or the DBP-25OHD complex, thereby preventing the urinary loss of these proteins and 25OHD. The total concentrations of 25OHD and 1,25(OH)2D in DBP null mice or humans are extremely low but calcium and bone homeostasis remain normal. This is the strongest argument for claiming that the “free hormone hypothesis” also applies to the vitamin D hormone, 1,25(OH)2D. DBP also transports fatty acids, and can play a role in the immune system. DBP is genetically very polymorphic with three frequent alleles (DBP/GC 1f, 1s, and 2) but in total more than 120 different variants but its health consequences, if any, are not understood. A standardization of DBP assays is essential to further explore the role of DBP in physiology and diseases.
format Online
Article
Text
id pubmed-6965021
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-69650212020-01-29 Vitamin D Binding Protein: A Historic Overview Bouillon, Roger Schuit, Frans Antonio, Leen Rastinejad, Fraydoon Front Endocrinol (Lausanne) Endocrinology Vitamin D and all its metabolites are bound to a specific vitamin D binding protein, DBP. This protein was originally first discovered by its worldwide polymorphism and called Group-specific Component (GC). We now know that DBP and GC are the same protein and appeared early in the evolution of vertebrates. DBP is genetically the oldest member of the albuminoid family (including albumin, α-fetoprotein and afamin, all involved in transport of fatty acids or hormones). DBP has a single binding site for all vitamin D metabolites and has a high affinity for 25OHD and 1,25(OH)2D, thereby creating a large pool of circulating 25OHD, which prevents rapid vitamin D deficiency. DBP of higher vertebrates (not amphibians or reptiles) binds with very high affinity actin, thereby preventing the formation of polymeric actin fibrils in the circulation after tissue damage. Megalin is a cargo receptor and is together with cubilin needed to reabsorb DBP or the DBP-25OHD complex, thereby preventing the urinary loss of these proteins and 25OHD. The total concentrations of 25OHD and 1,25(OH)2D in DBP null mice or humans are extremely low but calcium and bone homeostasis remain normal. This is the strongest argument for claiming that the “free hormone hypothesis” also applies to the vitamin D hormone, 1,25(OH)2D. DBP also transports fatty acids, and can play a role in the immune system. DBP is genetically very polymorphic with three frequent alleles (DBP/GC 1f, 1s, and 2) but in total more than 120 different variants but its health consequences, if any, are not understood. A standardization of DBP assays is essential to further explore the role of DBP in physiology and diseases. Frontiers Media S.A. 2020-01-10 /pmc/articles/PMC6965021/ /pubmed/31998239 http://dx.doi.org/10.3389/fendo.2019.00910 Text en Copyright © 2020 Bouillon, Schuit, Antonio and Rastinejad. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Bouillon, Roger
Schuit, Frans
Antonio, Leen
Rastinejad, Fraydoon
Vitamin D Binding Protein: A Historic Overview
title Vitamin D Binding Protein: A Historic Overview
title_full Vitamin D Binding Protein: A Historic Overview
title_fullStr Vitamin D Binding Protein: A Historic Overview
title_full_unstemmed Vitamin D Binding Protein: A Historic Overview
title_short Vitamin D Binding Protein: A Historic Overview
title_sort vitamin d binding protein: a historic overview
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6965021/
https://www.ncbi.nlm.nih.gov/pubmed/31998239
http://dx.doi.org/10.3389/fendo.2019.00910
work_keys_str_mv AT bouillonroger vitamindbindingproteinahistoricoverview
AT schuitfrans vitamindbindingproteinahistoricoverview
AT antonioleen vitamindbindingproteinahistoricoverview
AT rastinejadfraydoon vitamindbindingproteinahistoricoverview