BIOCHEMICAL AND MOLECULAR STUDIES OF HUMAN METHENYLTETRAHYDROFOLATE SYNTHETASE

5-FormylH(4)folate is administered clinically under the name Leucovori n(TM) in association with the antineoplastic agent 5-fluorouracil (5-F U) to enhance the cytotoxic effects of 5-FU. The combination has been shown to be superior to 5-FU alone in the treatment of patients with m etastatic colorectal carcinoma, Methenyltetrahydrofolate synthetase (M THFS) catalyzes the transformation of 5-formyltetrahydrofolate to meth enylH(4)folate, which is the obligatory initial metabolic step prior t o the intracellular conversion of 5-formylH(4)folate to other reduced folates and the increase in intracellular folate pools required for 5- FU potentiation, In the following paper, we will summarize results of biochemical and molecular studies of human MTHFS.