Explanation of Vitamin K Cycle from NEJM (N Engl J Med 2013; 369:2345-2346December 12, 2013DOI: 10.1056/NEJMe1313682)
Vitamin K plays a single role in human biology — as a cofactor for the synthesis of γ-carboxyglutamic acid.
Importance of γ-carboxyglutamic acid?
1. component of at least 14 proteins (factor IX, factor VII, factor X, and prothrombin, protein C and protein S)
2. critical for the physiologic function of these proteins
We do not synthesize vitamin K, we ingest it in our diet.
Vit K Cycle:
1. vitamin K quinone reduced to the semiquinone –> cofactor required for conversion of glutamic-acid residues on the vitamin K–dependent proteins to γ-carboxyglutamic acid by vitamin K–dependent carboxylase
2. reaction produces Vitamin K epoxide –> converted back to vitamin K quinone by VKOR (vitamin K epoxide reductase)
Warfarin inhibits VKOR –> post-translational modification of the vitamin K–dependent blood-coagulation proteins is impaired –> reduced function of factors 10, 9, 7, 2 leads to delayed coagulation
Where the Protein products come in the cycle:
A more complicated diagram to illustrate the Vit K cycle:
Illustration showing where warfarin works in the Vit K cycle: