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Vitamin K 11 6pg - Vitamin K Spring 2011 Vitamin K...

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Vitamin K Spring 2011 Vitamin K Deficiency: Hemorraghing Animal Model • Danish discovery • Fat-free diets led to h h h k hemorraghing:chickens –Fat soluble factor named vitamin K –1943 Nobel Prize in Physiology and Medicine Menadione Phylloquinone Menaquinone-4 (MK-4) Menaquinone n+1 Vitamin K: Nomenclature • Quinones –Phylloquinone (provides most in US diet) • plant sources – green leafy vegetables and vegetable oils Vitamin K: Nomenclature • Menaquinone • Animal sources • Intestinal bacteria E coli B fragilis E. coli, B. fragilis • MK-4 is unique to the menaquinones – Alkylated from menadione present in animal feed – Also product of tissue conversion from dietary phyloquinone
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Vitamin K: Absorption • ~80% absorbed (synthetic) • Food bioavailability much lower than synthetic Vitamin K: Absorption –Small intestine –jejunum –Enhanced by fat, bile salts, pancreatic juice –Micelles –Chylomicrons lymph Vitamin K: Absorption • Large intestine –resident microflora synthesize & secrete menaquinone –absorption from colon limited Vitamin K Malabsorption • Absorption can be dramatically reduced in clinical conditions – Pancreatic insufficiency – Biliary insufficiency – Celiac disease Vitamin K: Transport • Chylomicron remnants deliver vitamin K to the liver • Transport in lipoproteins: –HDL, LDL, VLDL –very low blood concentrations • 0.15 -1.15 ng/ml Vitamin K Cellular Uptake • Tissue uptake would occur when chylomicron remnants are “cleared” by apolipoprotein E (apoE) receptors
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Vitamin K Storage, Excretion • Storage –Liver: predominately as i menaquinone –Limited storage (50-100 μ g) –Rapid turnover- short half-life •Body pool turnover in ~1.5 days • Excretion: feces, urine Vitamin K Function • Blood clotting and bone mineralization –vitamin K facilitates γ - vitamin K facilitates carboxyglutamatic acid (Gla) formation • proteins required for normal blood clotting and bone mineralization Vitamin K Function • Cofactor for a specific carboxylase –catalyzes the γ -carboxylation of peptide-bound glutamyl residues • Posttranslational carboxylation –specific glutamic acid residues in proteins –forms γ -carboxyglutamic acid (Gla) Vitamin K Dependent Carboxylase • Vitamin K hydroquinone and oxygen react to form a strong base – capable of abstracting a proton from the γ -carbon of the glutamate residue •which undergoes carboxylation to Gla
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• Carboxylase uses energy of vitamin K hydroquinone oxygenation to convert Glu to Gla in vitamin K Vitamin K Function –to convert Glu to Gla in vitamin K dependent proteins (VKDP) Vitamin K Dependent Blood Clotting Proteins Seven vitamin K dependent proteins involved in blood coagulation – Prothrombin (Factor II) – Factors VII, IX, X – Protein C – Protein S – Protein Z All are synthesized in the liver and have between 10 and 13 Gla residues Function of γ -Carboxyglutamated (Gla) Residues in Blood Coagulation Proteins • Gla residues enable Ca++ mediated
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