L-Methylfolate

Category: vitamin

Aliases: 5-mthf

Pharmacological Mechanism

Active folate (see folate one carbon); methyl donor for homocysteine remethylation.

Half-Life (t½)

PO: 3h

Dosing Guidelines

• PO: Typical 400 mcg (Range: 400–1000 mcg)

Target Organ Systems

• immune-hematologic
• nervous

Interactions

• B12 (methylcobalamin) (synergistic): Methionine synthase requires both. Low B12 with high 5-MTHF leads to 'methyl trap' and functional B12 deficiency.
• SAMe (synergistic): Folate / B12 cycle regenerates methionine from homocysteine, replenishing the SAMe pool.
• Folic Acid (synergistic): Same family — folic acid requires DHFR reduction, 5-MTHF is pre-reduced. Pick one; methylfolate preferred in MTHFR variants.

Pathways It Modulates

• Folate / one-carbon metabolism (substrate) — 5-methylTHF (bypasses MTHFR)
• Methionine cycle (cofactor) — homocysteine remethylation (methionine synthase)
• Serine de novo synthesis → one-carbon pool (cofactor) — active folate downstream of methylene-THF
• Transsulfuration → cysteine → glutathione (cofactor) — methionine remethylation (competing arm); affects homocysteine flux into transsulfuration

Chemical Identifiers

• PubChem CID: 135398561
• Formula: C20H25N7O6
• Molecular weight: 459.45 g/mol
• InChIKey: ZNOVTXRBGFNYRX-STQMWFEESA-N
• SMILES: CN1[C@H](CNC2=C1C(=O)NC(=N2)N)CNC3=CC=C(C=C3)C(=O)N[C@@H](CCC(=O)O)C(=O)O

References

• PMID 24494987
• PMID 22909145