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Review

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

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Research Division, Dynamical Business & Science Society–DBSS International SAS, Bogotá 110861, Colombia
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Research Group in Biochemistry and Molecular Biology, Universidad Distrital Francisco José de Caldas, Bogotá 110311, Colombia
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Research Group in Physical Activity, Sports and Health Sciences (GICAFS), Universidad de Córdoba, Montería 230002, Colombia
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kDNA Genomics®, Joxe Mari Korta Research Center, University of the Basque Country UPV/EHU, 20018 Donostia-San Sebastián, Spain
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Exercise & Sport Nutrition Laboratory, Human Clinical Research Facility, Texas A&M University, College Station, TX 77843, USA
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Physiology of Work and Exercise Response (POWER) Laboratory, Institute of Exercise Physiology and Rehabilitation Science, University of Central Florida, Orlando, FL 32816, USA
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Professional Program in Sport Training, School of Health and Sport Sciences, Fundación Universitaria del Área Andina, Bogotá 111221, Colombia
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Exercise and Performance Nutrition Laboratory, School of Health Sciences, Lindenwood University, Saint Charles, MO 63301, USA
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School of Kinesiology, Auburn University, Auburn, AL 36849, USA
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Edward via College of Osteopathic Medicine, Auburn, AL 36849, USA
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Department of Health, Nutrition and Exercise Science, Messiah University, Mechanicsburg, PA 17055, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Susanne Klaus
Nutrients 2021, 13(4), 1238; https://doi.org/10.3390/nu13041238
Received: 23 March 2021 / Revised: 1 April 2021 / Accepted: 7 April 2021 / Published: 9 April 2021
(This article belongs to the Special Issue Creatine Supplementation for Health and Clinical Diseases)
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 [Mg2+:ATP4−]2− and Cr to produce phosphocreatine (PCr) and [Mg2+:ADP3−]. 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. View Full-Text
Keywords: creatine kinase; energy metabolism; cell survival; bioinformatics; systems biology; cellular allostasis; dynamic biosensor creatine kinase; energy metabolism; cell survival; bioinformatics; systems biology; cellular allostasis; dynamic biosensor
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MDPI and ACS Style

Bonilla, D.A.; Kreider, R.B.; Stout, J.R.; Forero, D.A.; Kerksick, C.M.; Roberts, M.D.; Rawson, E.S. Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review. Nutrients 2021, 13, 1238. https://doi.org/10.3390/nu13041238

AMA Style

Bonilla DA, Kreider RB, Stout JR, Forero DA, Kerksick CM, Roberts MD, Rawson ES. Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review. Nutrients. 2021; 13(4):1238. https://doi.org/10.3390/nu13041238

Chicago/Turabian Style

Bonilla, Diego A., Richard B. Kreider, Jeffrey R. Stout, Diego A. Forero, Chad M. Kerksick, Michael D. Roberts, and Eric S. Rawson 2021. "Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review" Nutrients 13, no. 4: 1238. https://doi.org/10.3390/nu13041238

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