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©2013 UpToDate ® Print Email 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. Reproduced with permission from Tefferi, A, Pruthi, RK. The Biochemical Basis of Cobalamin Deficiency. Mayo Clin Proc 1994; 69:181