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A Population Model of Folate-Mediated One-Carbon Metabolism

Background: Previous mathematical models for hepatic and tissue one-carbon metabolism have been combined and extended to include a blood plasma compartment. We use this model to study how the concentrations of metabolites that can be measured in the plasma are related to their respective intracellul...

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Autores principales: Duncan, Tanya M., Reed, Michael C., Nijhout, H. Frederik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738981/
https://www.ncbi.nlm.nih.gov/pubmed/23857220
http://dx.doi.org/10.3390/nu5072457
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author Duncan, Tanya M.
Reed, Michael C.
Nijhout, H. Frederik
author_facet Duncan, Tanya M.
Reed, Michael C.
Nijhout, H. Frederik
author_sort Duncan, Tanya M.
collection PubMed
description Background: Previous mathematical models for hepatic and tissue one-carbon metabolism have been combined and extended to include a blood plasma compartment. We use this model to study how the concentrations of metabolites that can be measured in the plasma are related to their respective intracellular concentrations. Methods: The model consists of a set of ordinary differential equations, one for each metabolite in each compartment, and kinetic equations for metabolism and for transport between compartments. The model was validated by comparison to a variety of experimental data such as the methionine load test and variation in folate intake. We further extended this model by introducing random and systematic variation in enzyme activity. Outcomes and Conclusions: A database of 10,000 virtual individuals was generated, each with a quantitatively different one-carbon metabolism. Our population has distributions of folate and homocysteine in the plasma and tissues that are similar to those found in the NHANES data. The model reproduces many other sets of clinical data. We show that tissue and plasma folate is highly correlated, but liver and plasma folate much less so. Oxidative stress increases the plasma S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) ratio. We show that many relationships among variables are nonlinear and in many cases we provide explanations. Sampling of subpopulations produces dramatically different apparent associations among variables. The model can be used to simulate populations with polymorphisms in genes for folate metabolism and variations in dietary input.
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spelling pubmed-37389812013-08-09 A Population Model of Folate-Mediated One-Carbon Metabolism Duncan, Tanya M. Reed, Michael C. Nijhout, H. Frederik Nutrients Article Background: Previous mathematical models for hepatic and tissue one-carbon metabolism have been combined and extended to include a blood plasma compartment. We use this model to study how the concentrations of metabolites that can be measured in the plasma are related to their respective intracellular concentrations. Methods: The model consists of a set of ordinary differential equations, one for each metabolite in each compartment, and kinetic equations for metabolism and for transport between compartments. The model was validated by comparison to a variety of experimental data such as the methionine load test and variation in folate intake. We further extended this model by introducing random and systematic variation in enzyme activity. Outcomes and Conclusions: A database of 10,000 virtual individuals was generated, each with a quantitatively different one-carbon metabolism. Our population has distributions of folate and homocysteine in the plasma and tissues that are similar to those found in the NHANES data. The model reproduces many other sets of clinical data. We show that tissue and plasma folate is highly correlated, but liver and plasma folate much less so. Oxidative stress increases the plasma S-adenosylmethionine/S-adenosylhomocysteine (SAM/SAH) ratio. We show that many relationships among variables are nonlinear and in many cases we provide explanations. Sampling of subpopulations produces dramatically different apparent associations among variables. The model can be used to simulate populations with polymorphisms in genes for folate metabolism and variations in dietary input. MDPI 2013-07-05 /pmc/articles/PMC3738981/ /pubmed/23857220 http://dx.doi.org/10.3390/nu5072457 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Duncan, Tanya M.
Reed, Michael C.
Nijhout, H. Frederik
A Population Model of Folate-Mediated One-Carbon Metabolism
title A Population Model of Folate-Mediated One-Carbon Metabolism
title_full A Population Model of Folate-Mediated One-Carbon Metabolism
title_fullStr A Population Model of Folate-Mediated One-Carbon Metabolism
title_full_unstemmed A Population Model of Folate-Mediated One-Carbon Metabolism
title_short A Population Model of Folate-Mediated One-Carbon Metabolism
title_sort population model of folate-mediated one-carbon metabolism
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3738981/
https://www.ncbi.nlm.nih.gov/pubmed/23857220
http://dx.doi.org/10.3390/nu5072457
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