Sandbox Reserved 1709: Difference between revisions
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== Introduction== | == Introduction== | ||
=== Biological Role === | === Biological Role === | ||
<scene name='90/906893/Vkor_structure/1'>Vitamin K epoxide reductase</scene> (VKOR) is a reducing enzyme composed of 4-helices that spans the endoplasmic reticulum as a transmembrane protein<ref>DOI 10.1126/science.abc5667</ref>. Its enzymatic role is reducing <scene name='90/906893/Vkor_with_ko/1'>vitamin K epoxide</scene> (KO) to Vitamin K Hydroquinone (KH2)<ref>DOI 10.1021/bi700527j</ref> (Figure 1). The mechanism first occurs through the binding KO and using two cysteine residues to reduce KO into [https://en.wikipedia.org/wiki/Vitamin_K Vitamin K]. Then, a second pair of cysteine residues will reduce Vitamin K into the final product, KH2 (Figure 1). One of VKORs primary roles is to assist in blood coagulation through this KH2 regeneration mechanism.[[Image:VKOR_mechanism_2D.png|400 px|right|thumb|Figure 1. Mechanism of KO reduction into KH2.]] With Vitamin K as a cofactor, the [https://www.britannica.com/science/bleeding/The-extrinsic-pathway-of-blood-coagulation#ref64617 γ-carboxylase] enzyme will enact post-translational modification on KH2, oxidizing it back to KO. The oxidation of KH2 by γ-carboxylase is coupled with the carboxylation of a glutamate residue to form γ-carboxyglutamate. The coupling of this oxidation and carboxylation will activate several clotting factors in the coagulation cascade. | <scene name='90/906893/Vkor_structure/1'>Vitamin K epoxide reductase</scene> (VKOR) is a reducing enzyme composed of 4-helices that spans the endoplasmic reticulum as a transmembrane protein<ref>DOI 10.1126/science.abc5667</ref>. Its enzymatic role is reducing <scene name='90/906893/Vkor_with_ko/1'>vitamin K epoxide</scene> (KO) to Vitamin K Hydroquinone (KH2)<ref>DOI 10.1021/bi700527j</ref> (Figure 1). The mechanism first occurs through the binding KO and using two cysteine residues to reduce KO into [https://en.wikipedia.org/wiki/Vitamin_K Vitamin K]. Then, a second pair of cysteine residues will reduce Vitamin K into the final product, KH2 (Figure 1). One of VKORs primary roles is to assist in blood coagulation through this KH2 regeneration mechanism.[[Image:VKOR_mechanism_2D.png|400 px|right|thumb|Figure 1. Mechanism of KO reduction into KH2.]] With Vitamin K as a cofactor, the [https://www.britannica.com/science/bleeding/The-extrinsic-pathway-of-blood-coagulation#ref64617 γ-carboxylase] enzyme will enact post-translational modification on KH2, oxidizing it back to KO <ref>DOI 10.1074/jbc.RA120.015401</ref>. The oxidation of KH2 by γ-carboxylase is coupled with the carboxylation of a glutamate residue to form γ-carboxyglutamate. The coupling of this oxidation and carboxylation will activate several clotting factors in the coagulation cascade. | ||
=== Author's Notes === | === Author's Notes === | ||
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== Disease and Treatment == | == Disease and Treatment == | ||
=== Afflictions === | === Afflictions === | ||
Since activated Vitamin K plays a crucial role in blood coagulation, defects in the function and enzymatic activity of VKOR may detrimentally effect on Vitamin K's ability to promote blood clotting. Mutations in VKOR also increase susceptibility to vascular diseases, such as a stroke | Since activated Vitamin K plays a crucial role in blood coagulation, defects in the function and enzymatic activity of VKOR may detrimentally effect on Vitamin K's ability to promote blood clotting. Mutations in VKOR also increase susceptibility to vascular diseases, such as a stroke <ref>DOI 10.1161/CIRCULATIONAHA.105.580167</ref>. Vitamin K is also important in maintaining bone health with inactivity of VKOR linked to decreased bone density and osteoporosis osteoporosis<ref>DOI 10.7759/cureus.10816</ref>. | ||
=== Inhibition === | === Inhibition === | ||
[[Image:Warfarin.png |400 px| right| thumb | Figure 4. Structure of Warfarin.]] | [[Image:Warfarin.png |400 px| right| thumb | Figure 4. Structure of Warfarin.]] | ||
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== References == | == References == | ||
<references/> | <references/> | ||
