Metabolism of 10-formyldihydrofolate in humans.
The metabolism of 10-formyldihydrofolate is reviewed in this article. It had been the dogma that only tetrahydrofolates participate in enzyme-catalyzed one-carbon transfer reactions, until we showed in 1986 that 10-formyldihydrofolate serves as a substrate for aminoimidazolecarboxamide ribotide (AICAR) transformylase. Our data from studies in humans, cultured cells and bacteria as well as in vitro experiments indicate that the oxidation of 10-formyltetrahydrofolate to 10-formyldihydrofolate takes place, and 1 0-formyldihydrofolate is subsequently converted to dihydrofolate by AICAR transformylase. Dihydrofolate is then reduced to tetrahydrofolate and further metabolized by the well-established enzyme reactions. We believe that a new folate metabolic map is needed which incorporates the oxidation of 10-formyltetrahydrofolate and the utilization of 10-formyldihydrofolate by AICAR transformylase.
Baggott
J E
JE
Department of Nutrition Sciences, University of Alabama at Birmingham, 35294-3360, USA. matlocks@uab.edu
Tamura
T
T
D001419:Bacteria / Q000378:metabolism; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D006801:Humans; D019877:Hydroxymethyl and Formyl Transferases / Q000378:metabolism*; D002955:Leucovorin / Q000031:analogs & derivatives* / Q000378:metabolism*; D010084:Oxidation-Reduction; D051027:Phosphoribosylaminoimidazolecarboxamide Formyltransferase
C010161:10-formyltetrahydropteroylglutamic acid; C055914:10-formyldihydrofolate; D005492:Folic Acid; D019877:Hydroxymethyl and Formyl Transferases; D051027:Phosphoribosylaminoimidazolecarboxamide Formyltransferase; D002955:Leucovorin