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Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review

Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na(+)/Cl(−)-dependent Cr transporter (CRT). Once within cells, creatine...

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Autores principales: Bonilla, Diego A., Kreider, Richard B., Stout, Jeffrey R., Forero, Diego A., Kerksick, Chad M., Roberts, Michael D., Rawson, Eric S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070484/
https://www.ncbi.nlm.nih.gov/pubmed/33918657
http://dx.doi.org/10.3390/nu13041238
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author Bonilla, Diego A.
Kreider, Richard B.
Stout, Jeffrey R.
Forero, Diego A.
Kerksick, Chad M.
Roberts, Michael D.
Rawson, Eric S.
author_facet Bonilla, Diego A.
Kreider, Richard B.
Stout, Jeffrey R.
Forero, Diego A.
Kerksick, Chad M.
Roberts, Michael D.
Rawson, Eric S.
author_sort Bonilla, Diego A.
collection PubMed
description Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na(+)/Cl(−)-dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg(2+):ATP(4−)](2−) and Cr to produce phosphocreatine (PCr) and [Mg(2+):ADP(3−)](−). We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states.
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spelling pubmed-80704842021-04-26 Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review Bonilla, Diego A. Kreider, Richard B. Stout, Jeffrey R. Forero, Diego A. Kerksick, Chad M. Roberts, Michael D. Rawson, Eric S. Nutrients Review Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na(+)/Cl(−)-dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg(2+):ATP(4−)](2−) and Cr to produce phosphocreatine (PCr) and [Mg(2+):ADP(3−)](−). We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states. MDPI 2021-04-09 /pmc/articles/PMC8070484/ /pubmed/33918657 http://dx.doi.org/10.3390/nu13041238 Text en © 2021 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
Bonilla, Diego A.
Kreider, Richard B.
Stout, Jeffrey R.
Forero, Diego A.
Kerksick, Chad M.
Roberts, Michael D.
Rawson, Eric S.
Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review
title Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review
title_full Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review
title_fullStr Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review
title_full_unstemmed Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review
title_short Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review
title_sort metabolic basis of creatine in health and disease: a bioinformatics-assisted review
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070484/
https://www.ncbi.nlm.nih.gov/pubmed/33918657
http://dx.doi.org/10.3390/nu13041238
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