tetrahydrofolate interconversion

Definition

Target type: biologicalprocess

The chemical reactions and pathways by which one-carbon (C1) units are transferred between tetrahydrofolate molecules, to synthesise other tetrahydrofolate molecules. [GOC:yaf, PMID:1825999]

Tetrahydrofolate (THF) interconversion is a crucial biological process involving the conversion of folate, a vitamin B9, into its active coenzyme form, THF. This process occurs in multiple steps and plays a vital role in various metabolic pathways, including DNA synthesis, amino acid metabolism, and the synthesis of neurotransmitters.

**1. Reduction of Dihydrofolate to Tetrahydrofolate:**
The first step involves the reduction of dihydrofolate (DHF) to THF by the enzyme dihydrofolate reductase (DHFR). This step requires the reducing agent NADPH, which donates electrons to DHF.

**2. Interconversion of Tetrahydrofolate Derivatives:**
THF can exist in various forms, each carrying a specific one-carbon unit (C1). These C1 units are crucial for various metabolic reactions. The interconversion between different THF derivatives involves enzymatic reactions that transfer C1 units from one form to another. Key enzymes involved in this process include:

- **Serine hydroxymethyltransferase:** Converts serine to glycine, transferring a C1 unit from serine to THF, forming 5,10-methylene THF.
- **Thymidylate synthase:** Uses 5,10-methylene THF to convert deoxyuridylate (dUMP) to deoxythymidylate (dTMP), a crucial step in DNA synthesis.
- **Glycine cleavage enzyme:** Catalyzes the cleavage of glycine, generating a C1 unit that is transferred to THF, forming 5,10-methylene THF.

**3. Regeneration of Tetrahydrofolate:**
The various THF derivatives involved in metabolic reactions are eventually converted back to THF, ensuring continuous supply of the active coenzyme. This regeneration involves multiple enzymatic steps, including the reduction of dihydrofolate by DHFR.

**4. Importance of Tetrahydrofolate Interconversion:**
The interconversion of THF is essential for various biological processes, including:

- **DNA synthesis:** THF derivatives are required for the synthesis of thymine, a crucial component of DNA.
- **Amino acid metabolism:** THF plays a role in the synthesis and breakdown of amino acids, particularly glycine and serine.
- **Neurotransmitter synthesis:** THF is required for the synthesis of neurotransmitters like serotonin and dopamine.

Deficiencies in folate or disruptions in THF interconversion can lead to various health problems, including anemia, neural tube defects, and cardiovascular diseases.'
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Proteins (4)

Compounds (35)