Document Detail


The relationship between intracellular and plasma levels of folate and metabolites in the methionine cycle: a model.
MedLine Citation:
PMID:  23143835     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
SCOPE: Folate status and the status of the methionine cycle are typically assessed by measuring folate and metabolites in the plasma. It is assumed that plasma metabolite levels are proportional to their levels in tissues, but there is little information to support this assumption.
METHODS AND RESULTS: We developed a mathematical model, based on known kinetics of the methionine cycle in the liver and tissues, and the transport kinetics of metabolites into and out of the plasma. We use the model to explore the relationship between folate status and metabolite values in the plasma, the relationships between metabolite values and methylation capacity, the response to a methionine load, and the half-life of folate in plasma and tissues. We also use the model to study the effects of Down syndrome and oxidative stress on metabolite values in plasma and tissues. The model accurately reproduces measured metabolite values pre- and post-folate fortification. The model shows that a high acute intake of folate remains largely restricted to the plasma and is rapidly excreted; only a prolonged exposure to increased folate elevates tissue folate significantly.
CONCLUSION: The model accurately reproduces experimental and clinical findings and can serve as a platform to study, in silico, the relationships between metabolite values in tissues and plasma, and how these vary with methionine and B vitamin input, and with mutations in the genes for enzymes in the methionine cycle.
Authors:
Tanya M Duncan; Michael C Reed; H Frederik Nijhout
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-11-12
Journal Detail:
Title:  Molecular nutrition & food research     Volume:  57     ISSN:  1613-4133     ISO Abbreviation:  Mol Nutr Food Res     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-04     Completed Date:  2013-10-29     Revised Date:  2014-04-02    
Medline Journal Info:
Nlm Unique ID:  101231818     Medline TA:  Mol Nutr Food Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  628-36     Citation Subset:  IM    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Descriptor/Qualifier:
Cystathionine beta-Synthase / metabolism
Down Syndrome / blood
Folic Acid / administration & dosage,  blood*,  metabolism
Folic Acid Deficiency / blood
Half-Life
Homocysteine / blood
Humans
Methionine / metabolism*
Methylation
Models, Theoretical*
Nutrition Surveys
Nutritional Status
Oxidative Stress / drug effects
S-Adenosylmethionine / blood
Vitamin B 12 Deficiency / blood
Vitamin B Complex / administration & dosage
Vitamins / administration & dosage
Grant Support
ID/Acronym/Agency:
R01 ES019876/ES/NIEHS NIH HHS; R01 ES019876/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Vitamins; 0LVT1QZ0BA/Homocysteine; 12001-76-2/Vitamin B Complex; 7LP2MPO46S/S-Adenosylmethionine; 935E97BOY8/Folic Acid; AE28F7PNPL/Methionine; EC 4.2.1.22/Cystathionine beta-Synthase
Comments/Corrections

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