Cytosolic 5-formyltetrahydrofolate cyclo-ligase (MTHFS) catalyses the irreversible transformation of 5-formyltetrahydrofolate (5-formyl-THF) to 5,10-methenyltetrahydrofolate (5,10-methenyl-THF) (Dayan et al. 1995). MTHFS has higher affinity for the polyglutamate form of 5-formyl-THF (5-formyl-THFPG) (Bertrand et al. 1987). This reaction of tetrahydrofolate metabolism helps regulate carbon flow through the folate-dependent one-carbon metabolic network which is essential for growth and proliferation of cells.