Metabolism of [6R]-5-Formyltetrahydrofolate in Humans

TAMURA Tsunenobu

doi:10.20632/vso.78.11_539

The objective of this article is to review our recent findings on the bioactivity of orally administered unnatural isomer of [6R]-5-formyltetrahydrofolate in humans. It has been assumed that humans cannot utilize unnatural isomers of tetrahydrofolate, because they are enzymatically inactive. We tested a hypothesis that orally administered unnatural [6R]-5-formyltetrahydrofolate or [6S]-5,10-methenyltetrahydrofolate is bioactive in humans. Subjects were given independent oral doses of these unnatural folates and the natural [6S]-5-formyltetrahydrofolate to estimate the bioactivity of these folates. Folate concentrations in plasma samples, collected before and for 4 hours after the dose, were measured using microbiological assay, and folates in a 2-hour urine were also measured using HPLC. Based on these analyses, the unnatural folates were estimated to be 14〜50% bioactive compared to [6S]-5-formyltetrahydrofolate. A possible pathway explaining our findings includes the oxidation of the unnatural [6S]-lO-formyltetrahydrofolate, which is produced by two chemical reactions in the gastrointestinal tract, to 10-formyldihydrofolate, which is further metabolized to dihydrofolate by 5-amino-4-imidazolecarboxamide-ribotide transformylase. Dihydrofolate can then be metabolized to [6S]-5-methyltetrahydrofolate by well-established enzyme reactions. Furthermore, we analyzed the data published by various investigators to evaluate whether the orally administered [6RS]-5-formyltetrahydrofolate is only 50% bioactive, as would be predicted, or more than 50% bioactive. The analysis indicated that oral doses of [6RS]-5-formyltetrahydrofolate are about 40% more bioactive in humans than would be predicted.

Metabolism of [6R]-5-Formyltetrahydrofolate in Humans

Bibliographic Information

Search this article

Abstract

Journal

References(15)*help

Keywords

Details 詳細情報について

Export

Report a problem