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Biochemical and Molecular Studies of Human Methenyltetrahydrofolate Synthetase

Centre de Recherche, Hôtel-Dieu de Montréal, Montréal, Québec, Canada

Correspondence: Jacques Jolivet, M.D., Centre de Recherche, Hôtel-Dieu de Montréal, 3850 rue Saint-Urbain, Montréal, Québec, H2W 1T8, Canada. Telephone: 514-843-2700; Fax: 514-843-2715; e-mail: jolivetj{at}ERE.UMontreal.CA

5-FormylH₄folate is administered clinically under the name Leucovorin^TM in association with the antineoplastic agent 5-fluorouracil (5-FU) 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 metastatic colorectal carcinoma. Methenyltetrahydrofolate synthetase (MTHFS) catalyzes the transformation of 5-formyltetrahydrofolate to methenylH₄folate, which is the obligatory initial metabolic step prior to the intracellular conversion of 5-formylH₄folate 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.

Key Words. Leucovorin • Folate metabolism • 5-fluorouracil