Vitamin K Cycle

1. 1

   Glutamate residue + CO2 + O2 + vitamin K hydroquinone -> gamma-carboxyglutamate + vitamin K epoxide

   gamma-Glutamyl carboxylase (GGCX) 4.1.1.90 ST-0364 Irreversible/directional Vitamin K hydroquinone O2 CO2
   In Glutamate residue CO2 O2 Vitamin K hydroquinone

   Out gamma-carboxyglutamate Vitamin K epoxide
   › Notes

   Gla residues chelate Ca2+ and anchor factors II, VII, IX, X and proteins C, S and Z to phospholipid membranes; also osteocalcin and matrix Gla protein.

2. 2

   Vitamin K 2,3-epoxide -> vitamin K quinone

   Vitamin K epoxide reductase (VKORC1) 1.17.4.4 ST-0365 Irreversible/directional rate-limiting
   In Vitamin K 2,3-epoxide

   Out Vitamin K quinone
   › Notes

   The warfarin target. VKORC1 polymorphisms are a major determinant of warfarin dose requirement.

3. 3

   Vitamin K quinone + NAD(P)H -> vitamin K hydroquinone

   VKORC1 / NQO1 quinone reductase ST-0366 Irreversible/directional NAD(P)H
   In Vitamin K quinone NAD(P)H

   Out Vitamin K hydroquinone
   › Notes

   The NQO1-dependent bypass explains why high-dose vitamin K can overcome warfarin.

Showing all 3 steps.