Activity of 5, 10-Methenyltetrahydrofolate Synthetase in Rat Tissues and in Tumor Cell Lines

The enzyme 5,10-methenyltetrahydrofolate synthetase catalyzes the key enzymatic reaction in the pathway by which 5-formyl tetrahydrofolate (leucovorin) enters the folate coenzyme pool. The distribution of this enzyme in different organs and tumor cell lines was studied. This enzyme has a wide distribution among organs and tumor cell lines with highest levels of activity in liver and kidney. Tumor cell lines also contain significant levels of this enzyme activity. Thus, leucovorin can be converted to active folate coenzyme forms in organs and tumor cells, and does not require conversion in liver alone. The implications of these findings for leucovorin usage as “rescue’’ after methotrexate treatment or to augment fluoropyrimidine cytotoxicity are discussed.