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[Biochemistry](https://durgical.com/en/biochemistry/) · Molecule

# Folate (vitamin B9)

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

Updated 2026-11-01

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## 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.

## In detail

- 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.

**Also called**
Vitamin B9, Folic acid, Tetrahydrofolate (THF), 5-methyl-THF

**Formula**
C₁₉H₁₉N₇O₆

**PubChem**
[CID 135398658](https://pubchem.ncbi.nlm.nih.gov/compound/135398658)

## Structure

- 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.

## Clinical notes

- 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.

## Drugs that act here

- [Calcium folinate](https://durgical.com/en/pharmacology/calcium-folinate/)

## Related conditions

- [Megaloblastic anaemia (B12 or folate deficiency)](https://durgical.com/en/conditions/megaloblastic-anaemia/)
- [Spina bifida (myelomeningocele)](https://durgical.com/en/conditions/spina-bifida/)
- [Coeliac disease](https://durgical.com/en/conditions/coeliac-disease/)

## Related

- [Dihydrofolate reductase (DHFR)](https://durgical.com/en/biochemistry/enzymes/dihydrofolate-reductase/)
- [Thymidylate synthase](https://durgical.com/en/biochemistry/enzymes/thymidylate-synthase/)
- [Cobalamin (vitamin B12)](https://durgical.com/en/biochemistry/topics/cobalamin/)
- [Vitamin B6 (pyridoxal phosphate)](https://durgical.com/en/biochemistry/molecules/vitamin-b6/)

## Test yourself

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.

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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)](https://pubchem.ncbi.nlm.nih.gov/compound/135398658) (PubChem, NCBI, 2026) · Public domain; [Folic acid in diet: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/002408.htm) (MedlinePlus, US National Library of Medicine, 2026); [Folate-deficiency anemia: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/000551.htm) (MedlinePlus, US National Library of Medicine, 2026); [MTHFR gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/mthfr/) (MedlinePlus, US National Library of Medicine, 2026); [Folic Acid | Folate | MedlinePlus](https://medlineplus.gov/folicacid.html) (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).

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