Formaldehyde regulates tetrahydrofolate stability and thymidylate synthase catalysis

Tetrahydrofolic acid and formaldehyde are key human metabolites but their physiologically relevant chemistry is undefined. Our NMR studies confirm formaldehyde as a product of tetrahydrofolic acid degradation but also reveal their reaction regulates the stability of tetrahydrofolic acid. These obser...

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Bibliographic Details
Published inChemical communications (Cambridge, England) Vol. 57; no. 47; pp. 5778 - 5781
Main Authors Chen, Xiaolei, Chothia, Sara Y, Basran, Jaswir, Hopkinson, Richard J
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 10.06.2021
Subjects
Formaldehyde
Metabolites
NMR
Nuclear magnetic resonance
Stability
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Summary:Tetrahydrofolic acid and formaldehyde are key human metabolites but their physiologically relevant chemistry is undefined. Our NMR studies confirm formaldehyde as a product of tetrahydrofolic acid degradation but also reveal their reaction regulates the stability of tetrahydrofolic acid. These observations identify a novel non-enzymatic feedback mechanism regulating formaldehyde and folate metabolism that has important implications for folate-targeting chemotherapy in cancer and other diseases. NMR studies on the formation and stability of 5,10-methylenetetrahydrofolic acid reveal a non-enzymatic feedback mechanism mediated by formaldehyde.
Bibliography:Electronic supplementary information (ESI) available: Procedures for production of recombinant thymidylate synthase and NMR analyses. See DOI
10.1039/d1cc01425k
ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1359-7345
1364-548X
DOI:10.1039/d1cc01425k