Vitamin K Cycle and Coumadin

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

Simplified Diagram:

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: