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Metabolism of 10-formyldihydrofolate in humans

Review · human · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2001 · DOI 10.1016/s0753-3322(01)00093-2 · PMID 11686579

Plain-language summary

Paraphrased from the published abstract below — not a verdict on whether anything works.

This review discusses the metabolism of 10-formyldihydrofolate, describing studies in humans, cultured cells, and bacteria, plus in vitro experiments. The authors state that prior dogma held only tetrahydrofolates participate in enzyme-catalyzed one-carbon transfer reactions, until their 1986 work showed 10-formyldihydrofolate serves as a substrate for aminoimidazolecarboxamide ribotide (AICAR) transformylase. They describe data indicating 10-formyltetrahydrofolate is oxidized to 10-formyldihydrofolate, which is then converted to dihydrofolate by AICAR transformylase and subsequently reduced to tetrahydrofolate. The authors propose that a revised folate metabolic map is needed to incorporate this oxidation and utilization pathway. Species: human, plus cultured cells and bacteria.

Abstract

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.

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