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The Oncologist, Vol. 1, No. 4, 248–253, August 1996
© 1996 AlphaMed Press

ADVANCES IN CANCER TREATMENT: THE CHABNER SYMPOSIUM

Biochemical and Molecular Studies of Human Methenyltetrahydrofolate Synthetase

Jacques Jolivet, Alain Dayan, Myriam Beauchemin, Dounia Chahla, Aline Mamo, Richard Bertrand

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 LeucovorinTM 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




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D. Wu, Y. Li, G. Song, C. Cheng, R. Zhang, A. Joachimiak, N. Shaw, and Z.-J. Liu
Structural Basis for the Inhibition of Human 5,10-Methenyltetrahydrofolate Synthetase by N10-Substituted Folate Analogues
Cancer Res., September 15, 2009; 69(18): 7294 - 7301.
[Abstract] [Full Text] [PDF]


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