The vitamin K cycle.
Vitamin K is a collective term for lipid-like naphthoquinone derivatives synthesized only in eubacteria and plants and functioning as electron carriers in energy transduction pathways and as free radical scavengers maintaining intracellular redox homeostasis. Paradoxically, vitamin K is a required micronutrient in animals for protein posttranslational modification of some glutamate side chains to gamma-carboxyglutamate. The majority of gamma-carboxylated proteins function in blood coagulation. Vitamin K shuttles reducing equivalents as electrons between two enzymes: VKORC1, which is itself reduced by an unknown ER lumenal reductant in order to reduce vitamin K epoxide (K>O) to the quinone form (KH2); and gamma-glutamyl carboxylase, which catalyzes posttranslational gamma-carboxylation and oxidizes KH2 to K>O. This article reviews vitamin K synthesis and the vitamin K cycle, outlines physiological roles of various vitamin K-dependent, gamma-carboxylated proteins, and summarizes the current understanding of clinical phenotypes caused by genetic mutations affecting both enzymes of the vitamin K cycle.
Oldenburg
Johannes
J
Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, D-53105 Bonn, Germany.
Marinova
Milka
M
Müller-Reible
Clemens
C
Watzka
Matthias
M
D000818:Animals; D001777:Blood Coagulation; D002118:Calcium / Q000378:metabolism; D019735:Carbon-Carbon Ligases / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology / Q000627:therapeutic use; D006706:Homeostasis; D006801:Humans; D006899:Mixed Function Oxygenases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D010024:Osteoporosis; D014812:Vitamin K / Q000378:metabolism* / Q000502:physiology; D010837:Vitamin K 1 / Q000378:metabolism; D024482:Vitamin K 2 / Q000378:metabolism; D064417:Vitamin K Epoxide Reductases
D003374:Coumarins; D024482:Vitamin K 2; D014812:Vitamin K; D010837:Vitamin K 1; C030123:coumarin; D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase; D002118:Calcium