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.
Baggott
J E
JE
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Johanning
G L
GL
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