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
Loading the 3D model…
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.
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
Related conditions
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).
Educational information, not medical advice. For any symptom, see a health professional.
Sources: VKORC1: Vitamin K epoxide reductase complex subunit 1 (human) (UniProt, 2026); EC 1.17.4.4: vitamin-K-epoxide reductase (warfarin-sensitive) (ExPASy ENZYME, SIB Swiss Institute of Bioinformatics, 2026); 6WV3: Human VKOR with warfarin (RCSB Protein Data Bank, 2026); VKORC1 gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); WARFARIN SODIUM tablet (DailyMed, US National Library of Medicine, 2026); Warfarin: MedlinePlus Drug Information (MedlinePlus, US National Library of Medicine, 2026).
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.