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Pathway Description
Vitamin K Metabolism
Bos taurus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-10
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
Zimin AV, Delcher AL, Florea L, Kelley DR, Schatz MC, Puiu D, Hanrahan F, Pertea G, Van Tassell CP, Sonstegard TS, Marcais G, Roberts M, Subramanian P, Yorke JA, Salzberg SL: A whole-genome assembly of the domestic cow, Bos taurus. Genome Biol. 2009;10(4):R42. doi: 10.1186/gb-2009-10-4-r42. Epub 2009 Apr 24.
Pubmed: 19393038
Irwin DM, Robertson KA, MacGillivray RT: Structure and evolution of the bovine prothrombin gene. J Mol Biol. 1988 Mar 5;200(1):31-45. doi: 10.1016/0022-2836(88)90331-2.
Pubmed: 3379642
MacGillivray RT, Davie EW: Characterization of bovine prothrombin mRNA and its translation product. Biochemistry. 1984 Apr 10;23(8):1626-34. doi: 10.1021/bi00303a007.
Pubmed: 6326805
Irwin DM, Ahern KG, Pearson GD, MacGillivray RT: Characterization of the bovine prothrombin gene. Biochemistry. 1985 Nov 19;24(24):6854-61. doi: 10.1021/bi00345a018.
Pubmed: 3000440
Rehemtulla A, Roth DA, Wasley LC, Kuliopulos A, Walsh CT, Furie B, Furie BC, Kaufman RJ: In vitro and in vivo functional characterization of bovine vitamin K-dependent gamma-carboxylase expressed in Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4611-5. doi: 10.1073/pnas.90.10.4611.
Pubmed: 8506307
Wu SM, Cheung WF, Frazier D, Stafford DW: Cloning and expression of the cDNA for human gamma-glutamyl carboxylase. Science. 1991 Dec 13;254(5038):1634-6. doi: 10.1126/science.1749935.
Pubmed: 1749935
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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