Vit k 3 pp - Vitamin K Spring 2011 Vitamin K Deficiency:...

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Vitamin K Spring 2011 Vitamin K Deficiency: Hemorraghing Animal Model •Dan ish d iscovery • Fat-free diets led to hemorraghing:chickens – Fat soluble factor named vitamin K – 1943 Nobel Prize in Physiology and Medicine Menadione Phylloquinone
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Vitamin K: Nomenclature • Quinones – Phylloquinone (provides most in US diet diet) • plant sources – green leafy vegetables and vegetable oils Vitamin K: Nomenclature • Menaquinone • Animal sources • Intestinal bacteria EcoliBfragilis 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
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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 menaquinone –Limited storage (50-100 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 - 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 -carboxylation of peptide-bound glutamyl residues • Posttranslational carboxylation – specific glutamic acid residues in proteins –forms -carboxyglutamic acid (Gla)
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Vitamin K Dependent Carboxylase • Vitamin K hydroquinone and oxygen react to form a strong base – capable of abstracting a proton from the -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 –P ro te in C –P
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Vit k 3 pp - Vitamin K Spring 2011 Vitamin K Deficiency:...

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