Table of Contents
What is VKORC1 gene?
The VKORC1 gene provides instructions for making a vitamin K epoxide reductase enzyme. The VKORC1 enzyme is made primarily in the liver. It spans the membrane of a cellular structure called the endoplasmic reticulum, which is involved with protein processing and transport.
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.
How does a mutation of VKORC1 affect the sensitivity of warfarin?
Certain VKORC1 gene polymorphisms decrease the amount of functional VKORC1 enzyme available to help activate clotting proteins. Individuals develop warfarin sensitivity because a lower warfarin dose is needed to inhibit the VKORC1 enzyme, as there is less functional enzyme that needs to be suppressed.
What does CYP2C9 do to warfarin?
A patient’s CYP2C9 and VKORC1 genotype can be used to help determine the optimal starting dose of warfarin. The CYP2C9 gene encodes one of the main enzymes involved in the metabolism of warfarin. Several variant CYP2C9 alleles are associated with reduced enzyme activity and lower clearance rates of warfarin.
How does warfarin inhibit VKORC1?
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.
What is the chromosomal location of the VKORC1 gene?
chromosome 16
Gene. The human gene is located on chromosome 16.
What are the genes that metabolize warfarin?
Many genes are involved in the metabolism of warfarin and in determining the drug’s effects in the body. Certain common changes (polymorphisms) in the CYP2C9 and VKORC1 genes account for most of the variation in warfarin metabolism due to genetic factors.
How does VKORC1 affect warfarin?
Are there different types of Factor 5?
Because each protein in our body is made by two different genes (one inherited from Mom, one inherited from Dad), there are two types of FVL: “heterozygous” (in which only one mutated copy of the F5 gene was inherited, either from the mother or the father), and “homozygous” (in which two mutated copies were inherited.
Is warfarin a CYP450 inhibitor?
Drugs may be metabolized by only one CYP450 enzyme (e.g., metoprolol by CYP2D6) or by multiple enzymes (e.g., warfarin [Coumadin] by CYP1A2, CYP2D6, and CYP3A4). Drugs that cause CYP450 metabolic drug interactions are referred to as either inhibitors or inducers (Table 110,14–16 ).
How does warfarin inhibit vitamin K?
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. VKORC1 produces KH2 in 2 reactions: reduction of vitamin K epoxide (KO) to quinone (K), and then KH2.
What does the CYP1A2 gene do?
CYP1A2 is an important detox enzyme that breaks down toxic chemicals, drugs, hormones, and other products of metabolism in order to eliminate them from your body. It’s found mainly in the liver [1, 2]. This enzyme is one of the cytochrome P450 monooxygenases (CYPs).
What happens when CYP1A2 is inhibited?
CYP1A2 Inhibitors Drugs that inhibit CYP1A2 will predictablyincrease the plasma concentrationsof the medications listed inTable 1, and in some cases adverseoutcomes will occur.
Where is Vitamin K epoxide reductase found?
5.1 Vitamin K epoxide reductase complex 1 (VKORC1) The VKORC1 gene, located on chromosome 16, is an important PD gene involved in warfarin dosage requirement variations. This reductase complex is targeted directly by coumarins considered as vitamin K antagonists (Jackson and Suttie, 1977).
What does the VKORC1 gene do?
The VKORC1gene encodes the VKORC1 (vitamin K epoxide reductase) protein, which is a key enzyme in the vitamin K cycle [1,2]. VKORC1 is a 163 amino acid integral membrane protein associated with the endoplasmic reticulum and VKORC1 mRNA is broadly expressed in many different tissues [3].
What does VKOR stand for?
Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.
Is vitamin K epOxide Reductase complex subunit 1 a key enzyme?
This review is focused on biochemical and genetic aspects of a recently characterized key enzyme of the cycle named vitamin K epoxide reductase complex subunit 1 (VKORC1). This 163-amino acid long protein (18 kDa) is responsible for vitamin K reduction.
Is VKORC1 a candidate gene for warfarin response variability?
Inappropriate dosing of warfarin has been associated with a substantial risk of both major and minor hemorrhage. As the pharmacological target of warfarin, VKORC1 is considered a candidate gene for the variability in warfarin response.