The metabolic functions and mechanism of action of vitamin K.
Vitamin K functions in animal cells as the cofactor of the enzyme vitamin K-dependent carboxylase which catalyzes the post-translational formation of gamma-carboxyglutamyl (Gla) residues in specific vitamin K-dependent proteins. These proteins include four blood coagulation factors (prothrombin and Factors VII, IX and X), other plasma proteins (protein C, protein S and protein Z), two proteins from bone (osteocalcin or bone Gla-protein and matrix Gla-protein), and other proteins from lung, kidney, spleen, testis, placenta and other tissues. In the proteins involved in blood coagulation the Gla residues are mandatory for the activation of the inactive proenzymes; this process occurs on phospholipid surfaces to which the proenzymes are bound via Gla residues and calcium ions. The energy needed in the carboxylation reaction is obtained from the oxidation of vitamin K hydroquinone to 2,3-epoxide of the vitamin. Specific enzymes, vitamin K epoxide reductase and vitamin K quinone reductases, catalyze consecutive reactions in which the vitamin K hydroquinone is regenerated, thus allowing continued use of the vitamin K molecule for the carboxylations. The oral anticoagulants, derivatives of 4-hydroxycoumarin and indan-1,3-dione, used as therapeutic agents in thromboembolic disease, are antagonists to vitamin K preventing the catalytic use of vitamin K in the carboxylations by irreversibly inhibiting vitamin K epoxide reductase.
Uotila
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Department of Clinical Chemistry, University of Helsinki, Finland.
D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D001798:Blood Proteins / Q000502:physiology; D019735:Carbon-Carbon Ligases; D006801:Humans; D008025:Ligases / Q000737:chemistry / Q000302:isolation & purification; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D011808:Quinone Reductases / Q000737:chemistry / Q000378:metabolism; D014812:Vitamin K / Q000378:metabolism / Q000502:physiology*; D064417:Vitamin K Epoxide Reductases
D001798:Blood Proteins; D014812:Vitamin K; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases; D011808:Quinone Reductases; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase