Vitamin K Flashcards
Vit K: Henrik Dam
Chicks fed diets extracted with organic solvents displayed hemorrhages and long blood-clotted times
Vit K: Hoist and Holbrook
Find that cabbage can prevent the clotting defect
Vit K: Dam
Shows that the clotting defect is corrected by fat-soluble factor in green leaves, distinct from Vitamins A, C, D or E; proposed name Vitamin K (Koagulation in danish/German)
Vit K:Dam, Edward Doisy and Paul Karrer
Determined the structure
Vit K: Nobel prize
Dam for discovery and Doisy for chemical nature
Vit K: Structure
Phylloquinone– 2-methyl-1-4-napthoquinone & isoprenoid side chain.
Vit K: Plant biologically active form
phylloquinone- vitamin K1
Vit K: Bacteria active forms
Menaquinone-4 and -7
Vit K: Synthetic active form
Menadione- only water soluble
Vit K: Fermented cheeses
Menaquinone-4
Vit K: Fermented soy products
Menaquinone-7
Vit K:Food Sources
Cabbage,. Pretty widely distributed around except for fruits* Deficiency is very uncommopn
Vit K: Absorption
Same as Vitamin A. BUT IN THE JEJUNUM* Phylloquinone/ Menaquinone w/ bile is made into a micelle and brought into the intestinal cell then made into a chylomicron and enters the lymph system.
Vit K: Hepatic metabolism
Chylomicron remnant w/ phyllo/ mena into the hepatocyte made into menadione if not already menaquinone with alkylation with a isoprenyl group. Mena/ Phyllo and VLDL components are combined to enter transport to the peripheral tissues.
Vit K: Transport and tissue uptake
Transported in lioproteins VLDL –> LDL –> HDL. Lipoproteins bind to lipoprotein receptors (apo receptor) on cell surface of tissues. Lipoproteins taken up via receptor-mediated endocytosis. Vitamin K acquired by cell.
Vit K: Storage and secretion.
Storage: Liver: predominately as menaquinone. Limited storage (50-100 micrograms). Rapid turnover- short half-life— body pool turnover in ~1.5 days…. Don’t need to store much because how much is distributed.
Vit K: Excretion
Feces and urine.
Vit K: Functions
Necessary for posttranslational carboxylation of glutamic acid residues in proteins to form gamma-carboxyglutamic acid residues (Gla). Gla residues enable the protein to bind to calcium and interact with other proteins— interactions necessary for blood clotting and bone mineralization.
Vit K: Blood clotting proteins
Seven vitamin K-dependent proteins are involved in blood coagulation: Factor II (prothrombin), VII, IX, X ((promote coagulation)). Protein C, S, and Z (inhibit coagulation). All are synthesized in the liver and have between 10 and 13 Gla residues.
Vit K: Function of Gla residues
Gla residues enable Ca++ mediated binding of the proteins to the NEGATIVELY charged phospholipid surfaces- provided by blood platelets and endothelial cells at the site of injury… Gla-containg blood proteins are zymogen forms of serine proteases– prothrombin and factors VII, IX, X participate in formation of fibrin clot.
Vit K: Final steps in blood clotting
- A series of reactions generates the inactive clotting factor X. 2. Vitamin K and calcium activate inactive clotting factors to make them active (designated by a lower case a). 3. Active clotting factor Xa converts prothrombin to thrombin. 4. Thrombin and fibrin stabilizing factor XIIIa form fibrin which aggregates to produce an insoluble clot and stops bleeding.
Vit K: Vitamin K dependent clotting factors
IX, X, IXa, VIIa, Xa, VII, Prothrombin (factor II) and Thrombin (factor IIa).
Vit K: Prothrombin time test
In vitro test of vitamin K status. Measures time required for a fibrin clot to form after adding calcium and other substrates and other substances to citrated plasma. Normal time= 11-14s… >25s are associated with major bleeding and vitamin K deficiency.
Vit K: Antagonists
Dicumarol. Warfarin (brand name= coumadin). Used as therapy to prevent thromboembolisms (such as stroke, myocardial infarction). Warfarin also used as rat poison. Anticoagulant.
