10-Formyltetrahydrofolate Explained

10-Formyltetrahydrofolate (10-CHO-THF) is a form of tetrahydrofolate that acts as a donor of formyl groups in anabolism. In these reactions 10-CHO-THF is used as a substrate in formyltransferase reactions.

Functions

Two equivalents of 10-CHO-THF are required in purine biosynthesis through the pentose phosphate pathway, where 10-CHO-THF is a substrate for phosphoribosylaminoimidazolecarboxamide formyltransferase.

10-CHO-THF is required for the formylation of methionyl-tRNA formyltransferase to give fMet-tRNA.^[1]

Formation from methenyltetrahydrofolate

10-CHO-THF is produced from methylenetetrahydrofolate (CH₂H₄F) via a two step process. The first step generates 5,10-methenyltetrahydrofolate:^[2]

CH₂H₄F + NAD⁺

\rightleftharpoons CH₂H₂F + NADH + H⁺In the second step 5,10-methenyltetrahydrofolate undergoes hydrolysis:

CH₂H₂F + H₂O

\rightleftharpoons CHO-H₄F +The latter is equivalently written:

5,10-methenyltetrahydrofolate + H₂O

\rightleftharpoons 10-formyltetrahydrofolate

10-CHO-THF is also produced by the reaction

ATP + formate + tetrahydrofolate

\rightleftharpoons ADP + phosphate + 10-formyltetrahydrofolateThis reaction is catalyzed by formate-tetrahydrofolate ligase.

It can be converted back into tetrahydrofolate (THF) by formyltetrahydrofolate dehydrogenase or THF and formate by formyltetrahydrofolate deformylase.

Notes and References

1. Book: Voet. Donald. Fundamentals of Biochemistry: Life at the Molecular Level. 2016. Wiley. 978-1-118-91840-1. 1006–1007. 5th.
2. Methenyltetrahydrofolate Cyclohydrolase Is Rate Limiting for the Enzymatic Conversion of 10-Formyltetrahydrofolate to 5,10-Methylenetetrahydrofolate in Bifunctional Dehydrogenase-Cyclohydrolase Enzymes. Peter D. Pawelek . Robert E. MacKenzie. Biochemistry. 1998. 37. 4 . 1109–1115. 10.1021/bi971906t. 9454603.