Vitamin C Activates the Folate-Mediated One-Carbon Cycle in C2C12 Myoblasts

Antioxidants
Armando Alcazar MaganaJan F Stevens

Abstract

Vitamin C (L-ascorbic acid, AA) is an essential cellular antioxidant and cofactor for several α-ketoglutarate-dependent dioxygenases. As an antioxidant, AA interacts with vitamin E to control oxidative stress. While several reports suggest an interaction of AA with folate (vitamin B9) in animals and humans, little is known about the nature of the interaction and the underlying molecular mechanisms at the cellular level. We used an untargeted metabolomics approach to study the impact of AA on the metabolome of C2C12 myoblast cells. Compared to untreated cells, treatment of C2C12 cells with AA at 100 µM resulted in enhanced concentrations of folic acid (2.5-fold) and 5-methyl-tetrahydrofolate (5-methyl-THF, 10-fold increase) whereas the relative concentrations of 10-formyl-tetrahydrofolate decreased by >90% upon AA pretreatment, indicative of increased utilization for the biosynthesis of active THF metabolites. The impact of AA on the folate-mediated one-carbon cycle further manifested itself as an increase in the levels of methionine, whose formation from homocysteine is 5-methyl-THF dependent, and an increase in thymidine, whose formation from deoxyuridine monophosphate (dUMP) is dependent on 5,10-methylene-THF. These findings ...Continue Reading

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Citations

Jun 11, 2020·Antioxidants·Jacopo J V BrancaMatteo Becatti
Jul 30, 2020·Antioxidants·Luciano SasoVišnja Stepanić
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hanjo HellmannDuroy A Navarre

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