Mechanism of action of vitamin K: synthesis of gamma-carboxyglutamic acid.
Vitamin K (2-methyl-3-phytyl-1,4-naphthoquinone) is required for the synthesis of prothrombin, Factor VII, Factor IX, Factor X, and a number of newly discovered proteins. These plasma proteins participate in calcium-dependent phospholipid membrane interactions which are mediated through the presence of gamma-carboxyglutamyl residues in their amino-terminal region. Vitamin K is required for the postribosomal conversion of glutamyl residues in liver precursors of these proteins to gamma-carboxyglutamyl residues in the completed plasma proteins. In the absence of vitamin K, or in the presence of vitamin K antagonists, animals produce plasma forms which lack the carboxylated residue. These proteins are nonfunctional because of their lack of phospholipid interaction. The vitamin K-dependent carboxylase which carries out this reaction has been studied in rat liver microsomal preparations where it will carboxylate the endogenous precursor proteins. Low-molecular-weight glutamyl-containing peptide substrates, such as Phe-Leu-Glu-Glu-Leu, which are homologous to regions of the prothrombin precursor, will also serve as substrates for the detergent-solubilized enzyme. This enzyme has been shown to require the reduced form of the vitamin and O2 but no ATP or a biotin-containing protein for its activity. The same microsomal preparations will also convert vitamin K to its 2,3-epoxide, and it is possible that activity may be related to the role of the vitamin in driving the carboxylase reaction.
D015055:1-Carboxyglutamic Acid / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001710:Biotin / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D019735:Carbon-Carbon Ligases; D003374:Coumarins / Q000378:metabolism; D005971:Glutamates / Q000096:biosynthesis*; D006801:Humans; D008025:Ligases / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D008968:Molecular Conformation; D010100:Oxygen / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D013379:Substrate Specificity; D014812:Vitamin K / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D064417:Vitamin K Epoxide Reductases
D003374:Coumarins; D005971:Glutamates; D014812:Vitamin K; D002245:Carbon Dioxide; D015055:1-Carboxyglutamic Acid; D001710:Biotin; D000255:Adenosine Triphosphate; D011516:Prothrombin; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase; D010100:Oxygen