Vitamin K epoxide reductase complex subunit 1 (VKORC1) (VKORC1)

Vitamin K epoxide reductase complex subunit 1 (VKORC1) is a critical transmembrane enzyme located in the endoplasmic reticulum that facilitates the vitamin K cycle. It is responsible for the rate-limiting step of reducing vitamin K 2,3-epoxide to vitamin K quinone and subsequently to vitamin K hydroquinone (UniProt: Q9BQB6). This reduced form of vitamin K serves as an essential cofactor for the gamma-glutamyl carboxylase-mediated activation of several coagulation factors, including factors II, VII, IX, and X, as well as anticoagulant proteins C and S (StatPearls: NBK470313). By maintaining the pool of active vitamin K, VKORC1 plays a central role in the maintenance of hemostasis. It is the primary pharmacological target for coumarin-based anticoagulants like warfarin, which inhibit the enzyme to prevent the formation of active clotting factors (PubMed: 14712271). Genetic variations in the VKORC1 gene are significant determinants of individual sensitivity to anticoagulant therapy and are associated with conditions such as warfarin resistance or combined deficiency of vitamin K-dependent clotting factors (NCBI: PMC4640337).

Other names

VKORVitamin K epoxide reductase complex subunit 1VKORC1

Inhibition of the VKORC1 enzyme prevents the regeneration of reduced vitamin K hydroquinone from vitamin K epoxide, thereby halting the gamma-carboxylation and activation of vitamin K-dependent coagulation factors (StatPearls: NBK470313).