5metylTHF

5-methyl-tetrahydrofolate (5-MTHF), also called 5-methyl-THF, is the predominant circulating and biologically active form of folate in humans. It is produced in the folate cycle by the reduction of 5,10-methylenetetrahydrofolate and serves as a key methyl donor in one-carbon metabolism.

The main biological role of 5-MTHF is to donate a methyl group to homocysteine to form methionine, a reaction catalyzed by methionine synthase with vitamin B12 as a cofactor. Methionine is then converted to S-adenosylmethionine (SAM), the universal methyl donor involved in numerous methylation reactions, including DNA and histone methylation. Through this pathway, 5-MTHF links folate metabolism to epigenetic regulation and amino acid metabolism.

Biosynthesis and transport: 5-MTHF is formed from 5,10-methylenetetrahydrofolate by methylenetetrahydrofolate reductase (MTHFR). After formation, 5-MTHF is released into circulation and taken up by cells via folate transporters and receptors. It serves as an accessible source of one-carbon units for nucleotide synthesis and methylation reactions.

Clinical relevance: Common MTHFR gene variants can reduce the efficiency of converting 5,10-methylenetetrahydrofolate to 5-MTHF, potentially raising homocysteine levels. In such cases, supplementation with 5-MTHF is used as an alternative to folic acid, especially where impaired folate metabolism is a concern. As with other folates, adequate vitamin B12 status is important to prevent masking of deficiency symptoms.

Dietary sources include leafy greens, legumes, and fortified foods. Supplements are available in various forms, including calcium salts of 5-MTHF.