Effects of cobalamin and folic acid on DNA synthesis

Interdependent cofactor activity of cobalamin and folate in intracellular DNA synthesis and metabolism. The + signs indicate enhancement, and the - signs indicate inhibition. Demethylation of methyl-tetrahydrofolate (CH3-THF) to THF is a critical step in DNA synthesis because THF is the substrate for the enzyme that converts (THF)-1 to the polyglutamated form (THF)n. Only polyglutamated (THF)n participates in purine synthesis.