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Pathway Description
Vitamin K Metabolism
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-01-21
Last Updated: 2019-08-16
Vitamin K describes a group of lipophilic, hydrophobic vitamins that exist naturally in two forms (and synthetically in three others): vitamin K1, which is found in plants, and vitamin K2, which is synthesized by bacteria. Vitamin K is an important dietary component because it is necessary as a cofacter in the activation of vitamin K dependent proteins. Metabolism of vitamin K occurs mainly in the liver. In the first step, vitamin K is reduced to its quinone form by a quinone reductase such as NAD(P)H dehydrogenase. Reduced vitamin K is the form required to convert vitamin K dependent protein precursors to their active states. It acts as a cofactor to the integral membrane enzyme vitamin K-dependent gamma-carboxylase (along with water and carbon dioxide as co-substrates), which carboxylates glutamyl residues to gamma-carboxy-glutamic acid residues on certain proteins, activating them. Each converted glutamyl residue produces a molecule of vitamin K epoxide, and certain proteins may have more than one residue requiring carboxylation. To complete the cycle, the vitamin K epoxide is returned to vitamin K via the vitamin K epoxide reductase enzyme, also an integral membrane protein. The vitamin K dependent proteins include a number of important coagulation factors, such as prothrombin. Thus, warfarin and other coumarin drugs act as anticoagulants by blocking vitamin K epoxide reductase.
References
Vitamin K Metabolism References
Litwack G. ed. Vitamins and Hormones: Vitamin K. (2008) 78. New York: Academic Press, Elsevier
Stafford DW: The vitamin K cycle. J Thromb Haemost. 2005 Aug;3(8):1873-8. doi: 10.1111/j.1538-7836.2005.01419.x.
Pubmed: 16102054
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Pubmed: 20116943
Vasiliou V, Theurer MJ, Puga A, Reuter SF, Nebert DW: Mouse dioxin-inducible NAD(P)H: menadione oxidoreductase: NMO1 cDNA sequence and genetic differences in mRNA levels. Pharmacogenetics. 1994 Dec;4(6):341-8.
Pubmed: 7704040
Chen S, Clarke PE, Martino PA, Deng PS, Yeh CH, Lee TD, Prochaska HJ, Talalay P: Mouse liver NAD(P)H:quinone acceptor oxidoreductase: protein sequence analysis by tandem mass spectrometry, cDNA cloning, expression in Escherichia coli, and enzyme activity analysis. Protein Sci. 1994 Aug;3(8):1296-304. doi: 10.1002/pro.5560030816.
Pubmed: 7527260
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Pubmed: 21183079
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Pubmed: 16141072
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Pubmed: 15489334
Spohn G, Kleinridders A, Wunderlich FT, Watzka M, Zaucke F, Blumbach K, Geisen C, Seifried E, Muller C, Paulsson M, Bruning JC, Oldenburg J: VKORC1 deficiency in mice causes early postnatal lethality due to severe bleeding. Thromb Haemost. 2009 Jun;101(6):1044-50.
Pubmed: 19492146
Degen SJ, Schaefer LA, Jamison CS, Grant SG, Fitzgibbon JJ, Pai JA, Chapman VM, Elliott RW: Characterization of the cDNA coding for mouse prothrombin and localization of the gene on mouse chromosome 2. DNA Cell Biol. 1990 Sep;9(7):487-98. doi: 10.1089/dna.1990.9.487.
Pubmed: 2222810
Banfield DK, MacGillivray RT: Partial characterization of vertebrate prothrombin cDNAs: amplification and sequence analysis of the B chain of thrombin from nine different species. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2779-83. doi: 10.1073/pnas.89.7.2779.
Pubmed: 1557383
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0000464
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