10-Formyl-dihydrofolic acid is bioactive in human leukemia cells.
The bioactivity of 10-formyl-7,8-dihydrofolic acid and 10-formyl-folic acid was determined in human leukemia (CCRF-CEM) cells grown in a folate-depleted medium containing methotrexate. Excess 10-formyl-7,8-dihydrofolic acid, (but not 10-formyl folic acid) supported the growth of these cells, but it was less potent than5-formyl-5,6,7,8-tetrahydrofolic acid (a control). 10-formyl-7, 8-dihydrofolic acid (not 10-formyl folic acid) was active as substrate for aminoimidazole carboxamide ribotide transformylase and dihydrofolate reductase. This is the first experimental evidence that 10-formyl-7,8-dihydrofolic acid is a bioactive folate in mammalian cells. These experiments and several other lines of evidence in the literature suggest that 10-formyl-folic acid must be metabolized to bioactive folate by enteric bacteria before it can be utilized by the vertebrate host.
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
J E
JE
Baggott
G L
GL
Johanning
D000704:Analysis of Variance; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005492:Folic Acid / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D005494:Folic Acid Deficiency / Q000378:metabolism*; D006397:Hematinics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008727:Methotrexate / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D006397:Hematinics; D005492:Folic Acid; C120486:10-formyl-7,8-dihydrofolic acid; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate