| Vitamin K is necessary for blood coagulation
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| Figure 10.4 The structure and nomenclature of vitamin K. |
The name vitamin K refers to a group of related compounds, varying in the number of isoprenoid units in their side chain. Like vitamin E , the absorption of vitamin K depends on appropriate fat absorption. The structure, nomenclature and sources of the vitamin Ks are outlined in Figure 10.4. Vitamin K circulates as phylloquinone and its hepatic stores are in the form of manaquinones. It is required for the post-translational modification of several proteins (factors II, VII, IX, and X) in the coagulation cascade. All of these proteins are synthesized by the liver as inactive precursors and are activated by the carboxylation of specific glutamic acid
residues by a vitamin K-dependent enzyme (Fig. 10.5). Prothrombin (factor II) contains 10 of these carboxylated residues (Gla) and all are required for this protein's specific chelation of Ca2+ ions during its function in coagulation. Recently, other proteins containing vitamin K-dependent Gla residues, such as osteocalcin, have been identified in tissues. Vitamin K is widely distributed in nature: its dietary sources are green leafy vegetables also fruits, dairy products, and vegetable oils, cereals, and meats; its production by the intestinal microflora virtually ensures that dietary deficiency does not occur in man.
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| Vitamin K deficiency causes bleeding disorders
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| Deficiency of vitamin K is rare but may develop in those with liver disease, fat malabsorption, or in the newborn, and it is associated with bleeding disorders. Premature infants are especially at risk and may suffer from hemorrhagic disease of the newborn. The placental transfer of maternal vitamin K to the fetus is inefficient. Immediately after birth the circulating concentration decreases, but it recovers on absorption of food; this is possibly delayed in preterm infants. In addition, the gut of the newborn is sterile, so that the intestinal microflora does not provide a source of vitamin K for several days after birth.
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| Inhibitors of vitamin K action are valuable antithrombotic drugs
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| Figure 10.5 Vitamin K-mediated carboxylation of glutamate residues (Glu). This reaction produces carboxylated residues, which are required for Ca2+ chelation. Gla-γ-carboxyglutamate. |
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| Specific inhibitors of vitamin K-dependent carboxylation reactions are used in the treatment of thrombosis-related diseases, e.g. in patients with deep vein thrombosis and pulmonary thromboembolism, or patients with atrial fibrillation who are at risk of thrombosis. These are drugs of the dicoumarin group, e.g. warfarin, which inhibit the action of
vitamin K - probably via the mechanisms involved in the regeneration of the active hydroquinone. This drug is also used as rat poison and vitamin K is thus the antidote for human poisoning by this agent.
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