How does VKORC1 affect warfarin?

Warfarin exerts its anticoagulant effect by inhibiting the enzyme encoded by VKORC1, which catalyzes the conversion of vitamin K epoxide to the active reduced form of vitamin K, vitamin K hydroquinone.

Does warfarin inhibit VKORC1?

The anticoagulant warfarin inhibits the vitamin K oxidoreductase (VKORC1), which generates vitamin K hydroquinone (KH2) required for the carboxylation and consequent activation of vitamin K–dependent (VKD) proteins.

What is VKORC1 polymorphism?

Multiple variations (polymorphisms) in the VKORC1 gene have been associated with warfarin resistance, a condition in which individuals require higher doses of the drug warfarin than are usually prescribed. Warfarin is an anticoagulant, which means that it thins the blood and prevents blood clots from forming.

Can you be resistant to warfarin?

Warfarin resistance can be either acquired or hereditary. Possible causes of acquired resistance include enzymatic induction of warfarin metabolism by other drugs, enhanced dietary intake of vitamin K, noncompliance with therapy and hypothyroidism.

What does vitamin K epoxide reductase do?

Vitamin K epoxide reductase (VKOR) sustains blood coagulation by reducing vitamin K epoxide to the hydroquinone, an essential cofactor for the γ-glutamyl carboxylation of many clotting factors. The physiological redox partner of VKOR remains uncertain, but is likely a thioredoxin-like protein.

What is the function of CYP2C9?

Normal Function The CYP2C9 gene provides instructions for making an enzyme that is found in a cell structure called the endoplasmic reticulum, which is involved in protein processing and transport. The CYP2C9 enzyme breaks down (metabolizes) compounds including steroid hormones and fatty acids.

What drugs are metabolized by VKORC1?

3.2 VKORC1. Vitamin K epoxide reductase complex subunit 1, encoded by VKORC1 (chromosome 16), the drug target for the anticoagulants warfarin and acenocoumarol is used to prevent and treat thromboembolic cases. These drugs are metabolized primarily by the enzyme CYP2C9.

What is low warfarin sensitivity?

Description. Collapse Section. Warfarin sensitivity is a condition in which individuals have a low tolerance for the drug warfarin. Warfarin is an anticoagulant, which means that it thins the blood, preventing blood clots from forming.

What is warfarin resistance usually caused by?

The most common cause of warfarin resistance is non- compliance. Others include poor absorption, high vitamin K intake, hypersensitivity to vitamin K, and rapid drug deactivation. Patient education is necessary to improve compliance and to mitigate adverse effects of warfarin therapy, regardless of the dose.

How does warfarin inhibit vitamin K epoxide reductase?

Warfarin Inhibits Vitamin K Epoxide Reductase By Specifically Blocking at a Conformational and Redox State | Blood | American Society of Hematology.

Where is Vitamin K epoxide reductase?

The VKORC1 gene is located on chromosome 16 and contains 5126 base pairs arranged in three exons. VKORC1 variants are associated most commonly with warfarin sensitivity, but also with warfarin resistance, and they are implicated in multiple coagulation factor deficiency disorders.