Folate (vitamin B9) !

Folate carries one-carbon groups to build DNA; its lack causes megaloblastic anaemia and neural tube defects.

Updated 2026-11-01

Loading the 3D model…

Key facts

Active form: tetrahydrofolate (THF), which carries one-carbon units (methyl, methylene, formyl) to make purines and thymidylate.
Dihydrofolate reductase (DHFR) reduces folate to THF; methotrexate, trimethoprim and pyrimethamine inhibit it.
5-methyl-THF gives its methyl to homocysteine (methionine synthase, with B12): this is why both deficiencies raise homocysteine.
Stores last only a few months; taking folic acid before conception reduces neural tube defects.

Sources: green leaves (folium = leaf), legumes, liver, citrus; wheat flour is fortified with folic acid in Colombia and other countries of the region. Long cooking destroys folate.
Absorption: in the proximal jejunum, after the polyglutamate tail is removed; this is why coeliac disease reduces it.
Methylene-THF + dUMP → dTMP (thymidylate synthase): without this step rapidly dividing cells (bone marrow, mucosa, fetus) cannot copy their DNA properly.
MTHFR turns methylene-THF into 5-methyl-THF; its C677T variant lowers activity and raises homocysteine slightly.
Causes of deficiency: poor diet, alcoholism, pregnancy and breastfeeding, chronic haemolysis, malabsorption, drugs (methotrexate, phenytoin, trimethoprim).
Difference from B12: in folate deficiency methylmalonic acid is normal and there is no nerve damage.
Excess: high-dose folic acid can correct the anaemia of B12 deficiency without stopping the nerve damage, which keeps progressing.
Lab: serum folate (changes with recent diet) or red-cell folate (reflects months); raised homocysteine with normal methylmalonic acid.

Three parts: a pteridine ring, p-aminobenzoic acid (PABA) and glutamate. Sulphonamides compete with PABA in bacteria, which make their own folate.
THF has a reduced pteridine (four extra hydrogens); carbons are carried on nitrogens N5 and N10.

Folic acid is advised for every woman who could become pregnant, from before conception, to prevent spina bifida and anencephaly.
Methotrexate inhibits DHFR; folinic acid (leucovorin) supplies already-reduced THF and rescues healthy cells.
Megaloblastic anaemia from folate and from B12 look the same in blood: both must be measured before treating.

Think of the answer, then tap the question to see it.

Which enzyme turns folate into tetrahydrofolate, and which drugs inhibit it?

Dihydrofolate reductase; methotrexate (human), trimethoprim (bacterial) and pyrimethamine (parasite) inhibit it.

Why does folate deficiency cause megaloblastic anaemia?

Methylene-THF is lacking to make thymidylate; DNA synthesis lags while the cytoplasm matures, so precursors grow without dividing.

How do labs tell folate deficiency from B12 deficiency?

Both raise homocysteine, but only B12 deficiency raises methylmalonic acid.

Why is giving folic acid alone to a person with B12 deficiency dangerous?

It corrects the anaemia and hides the diagnosis while the nerve damage from lack of B12 keeps progressing.

Molecules are shown in their neutral form, as the databases deposit them; in the cell the acids and phosphates are ionised.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: Folic Acid (CID 135398658) (PubChem, NCBI, 2026) · Public domain; Folic acid in diet: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Folate-deficiency anemia: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); MTHFR gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Folic Acid | Folate | MedlinePlus (MedlinePlus, US National Library of Medicine, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.