Tetrahydrofolic acid

Tetrahydrofolic acid (THF) is a chemically reduced form of folic acid that serves as a cofactor in various metabolic processes. It plays a crucial role in the synthesis of nucleotides, the building blocks of DNA and RNA, and in the metabolism of amino acids, which are the building blocks of proteins. THF is involved in the transfer of one-carbon units in metabolic reactions, making it essential for the synthesis and repair of DNA and RNA, and for cell division and growth.

Biochemistry

THF is generated in the body from dietary folic acid through a series of enzymatic reductions. The enzyme dihydrofolate reductase (DHFR) catalyzes the reduction of dihydrofolate (DHF) to THF. THF can then accept various one-carbon units from donors such as serine, glycine, and formate, and transfer them to recipients in the synthesis of methionine, thymidine, and purine nucleotides. This process is vital for the synthesis of nucleic acids and for methylation reactions in cells.

Clinical Significance

THF and its derivatives are essential for cell growth and replication, making them particularly important in tissues with rapid cell turnover, such as the bone marrow and the developing fetus. Deficiencies in THF or in the enzymes involved in its metabolism can lead to various health issues, including megaloblastic anemia, a condition characterized by the production of abnormally large and immature red blood cells. Additionally, THF deficiency during pregnancy is associated with an increased risk of neural tube defects (NTDs) in the newborn, such as spina bifida and anencephaly.

To prevent these conditions, folic acid supplementation is recommended for women of childbearing age and during pregnancy. Moreover, certain drugs, such as methotrexate, which is used in the treatment of cancer and autoimmune diseases, inhibit DHFR, affecting THF synthesis and leading to side effects related to rapid cell division tissues.

Pharmacology

Given its role in DNA synthesis and repair, THF and its derivatives are explored for their potential in cancer treatment, as targeting folate metabolism can inhibit the proliferation of cancer cells. However, the therapeutic window is narrow, given the essential role of THF in normal cell function.

Dietary Sources and Supplementation

Dietary sources of folic acid, which is converted to THF in the body, include green leafy vegetables, fruits, nuts, and fortified foods. Despite the availability of folic acid in the diet, folic acid supplementation is often necessary for individuals at risk of deficiency, including pregnant women, individuals with alcohol dependence, and those with malabsorptive disorders.

Conclusion

Tetrahydrofolic acid is a vital biochemical molecule involved in numerous metabolic processes, including DNA and RNA synthesis, amino acid metabolism, and cell division. Its importance in human health is underscored by the consequences of its deficiency and the benefits of its supplementation in preventing certain congenital disorders and treating specific medical conditions.

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Tetrahydrofolic_acid

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  Tetrahydrofolic acid 3D spacefill

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  Dihydrofolic acid

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  5,10-Methylenetetrahydrofolic acid

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  10-Formyl-tetrahydrofolic acid