Biochemical and molecular studies of human methenyltetrahydrofolate synthetase.
5-FormylH4folate is administered clinically under the name Leucovorin 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-formyl-tetrahydrofolate 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.
Jolivet
J
J
Centre de Recherche, Hôtel-Dieu de Montréal, Québec, Canada.
Dayan
A
A
Beauchemin
M
M
Chahla
D
D
Mamo
A
A
Bertrand
R
R
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D019731:Carbon-Nitrogen Ligases; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008025:Ligases / Q000235:genetics / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D008025:Ligases; D019731:Carbon-Nitrogen Ligases; C021557:5,10-methenyltetrahydrofolate synthetase; D002955:Leucovorin; D005472:Fluorouracil