Dihydrofolic Acid (DH)

Dihydrofolic acid is a folic acid derivative which is converted to tetrahydrofolic acid by dihydrofolate reductase. Since tetrahydrofolate is needed to make both purines and pyrimidines, which are building blocks of DNA and RNA, dihydrofolate reductase is targeted by various drugs to prevent nucleic acid synthesis.

The dissociation constants (pKa) for the pteridine ring system of dihydrofolate (H2folate) have been redetermined, and those for dihydrobiopterin (H2biopterin) have been determined. Determination of the pKa for N5 of H2folate is complicated by the low solubility and instability of H2folate at pH 2-4, and other complicating factors. The redetermined value for the pKa of N5 of H2folate has implications for mechanistic models for dihydrofolate reductase, and revised kinetic constants have been calculated for one model.