5-Formiminotetrahydrofolate

5-Formiminotetrahydrofolate (5-FTHF) is a metabolite involved in the metabolism of amino acids and nucleic acids. It is a key component in the one-carbon metabolism pathway, which is essential for the synthesis of DNA and RNA.

Structure and Properties

5-Formiminotetrahydrofolate is a derivative of tetrahydrofolate, a form of the B-vitamin folate. It contains a formimino group (-NH=CH-) attached to the N5 position of the tetrahydrofolate molecule. This structure allows it to act as a one-carbon donor in various biochemical reactions.

Role in Metabolism

• In the body, 5-FTHF is produced from formiminoglutamate (FIGLU) in a reaction catalyzed by the enzyme formiminotransferase cyclodeaminase (FTCD). This reaction is part of the histidine degradation pathway, which breaks down histidine into glutamate and other metabolites.

• Once formed, 5-FTHF participates in the one-carbon metabolism pathway. Here, it donates its formimino group to a molecule of 5,10-methenyltetrahydrofolate, forming 5,10-methylenetetrahydrofolate and releasing ammonia. This reaction is catalyzed by the enzyme methenyltetrahydrofolate cyclohydrolase.

Clinical Significance

Deficiencies in the enzymes that metabolize 5-FTHF can lead to a buildup of FIGLU in the blood, a condition known as FIGLU-uria. This can cause symptoms such as intellectual disability, seizures, and anemia. Treatment typically involves supplementation with folic acid to boost the levels of tetrahydrofolate and its derivatives.

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See Also

• Folate
• One-carbon metabolism
• Formiminoglutamate
• Formiminotransferase cyclodeaminase
• Methenyltetrahydrofolate cyclohydrolase