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

# Vitamin K epoxide reductase (VKORC1)

VKORC1 recycles used vitamin K so the liver can keep activating clotting factors. Warfarin blocks it.

Updated 2026-11-01

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## Key facts

- Vitamin K cycle: γ-carboxylation of clotting proteins turns vitamin K hydroquinone into vitamin K 2,3-epoxide.
- VKORC1 reduces the epoxide back to vitamin K (quinone) and then to the hydroquinone, ready for another round.
- The electrons come from protein disulfide chemistry (a protein dithiol becomes a disulfide), not from NADPH.
- Vitamin K-dependent proteins: factors II, VII, IX and X and the anticoagulant proteins C and S.

**Also called**
VKOR

**EC number**
[1.17.4.4](https://www.enzyme-database.org/query.php?ec=1.17.4.4)

**Genes**
VKORC1

**Structure (PDB)**
[6WV3](https://www.rcsb.org/structure/6WV3)

## Structure

- A small membrane protein of the endoplasmic reticulum, 163 amino acids long, made mainly in the liver.
- Structure 6WV3 shows human VKOR with warfarin bound; warfarin locks the enzyme in a closed shape.

## Regulation

- Common variants change how much enzyme is made: the -1639G>A variant near the gene lowers it.
- Dietary vitamin K can bypass the block, which is why steady vitamin K intake matters during warfarin treatment.

## Inhibitors and toxins

- Warfarin and other 4-hydroxycoumarins (the S-enantiomer of warfarin is the more potent).
- Some rodenticides of the same family act on the same enzyme.

## Clinical notes

- Warfarin prevents and treats blood clots: atrial fibrillation, mechanical heart valves, deep vein thrombosis and pulmonary embolism.
- Its effect is followed with the prothrombin time reported as INR; serious bleeding is the main risk.
- VKORC1 and CYP2C9 variants help explain why people need very different amounts of warfarin; D36Y causes resistance.
- Vitamin K reverses the effect; the R98W variant causes a rare inherited lack of vitamin K-dependent factors.

## Drugs that act here

- [Warfarin](https://durgical.com/en/pharmacology/warfarin/)

## Related conditions

- [Atrial fibrillation](https://durgical.com/en/conditions/atrial-fibrillation/)
- [Deep vein thrombosis](https://durgical.com/en/conditions/deep-vein-thrombosis/)
- [Pulmonary embolism](https://durgical.com/en/conditions/pulmonary-embolism/)
- [Intracerebral haemorrhage](https://durgical.com/en/conditions/intracerebral-haemorrhage/)

## Test yourself

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

## What does VKORC1 do in the vitamin K cycle?

It reduces vitamin K 2,3-epoxide back to active vitamin K so carboxylation of clotting factors can go on.

## Which clotting factors depend on vitamin K?

Factors II, VII, IX and X, plus the anticoagulant proteins C and S.

## Why do some people need far less warfarin than others?

Variants such as VKORC1 -1639G>A make less enzyme; CYP2C9 variants slow warfarin breakdown.

## What reverses the effect of warfarin?

Vitamin K (and, in serious bleeding, replacing clotting factors).

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

Sources: [VKORC1: Vitamin K epoxide reductase complex subunit 1 (human)](https://rest.uniprot.org/uniprotkb/Q9BQB6.txt) (UniProt, 2026); [EC 1.17.4.4: vitamin-K-epoxide reductase (warfarin-sensitive)](https://enzyme.expasy.org/EC/1.17.4.4) (ExPASy ENZYME, SIB Swiss Institute of Bioinformatics, 2026); [6WV3: Human VKOR with warfarin](https://www.rcsb.org/structure/6WV3) (RCSB Protein Data Bank, 2026); [VKORC1 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/vkorc1/) (MedlinePlus, US National Library of Medicine, 2026); [WARFARIN SODIUM tablet](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8ad881e0-ca41-42ad-9d7d-eb85b3a30af0) (DailyMed, US National Library of Medicine, 2026); [Warfarin: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682277.html) (MedlinePlus, US National Library of Medicine, 2026).

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Source: https://durgical.com/en/biochemistry/enzymes/vitamin-k-epoxide-reductase/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/vitamin-k-epoxide-reductase/