Vitamin K

Question 1

Vit K: Henrik Dam

Answer 1

Chicks fed diets extracted with organic solvents displayed hemorrhages and long blood-clotted times

Question 2

Vit K: Hoist and Holbrook

Answer 2

Find that cabbage can prevent the clotting defect

Question 3

Vit K: Dam

Answer 3

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)

Question 4

Vit K:Dam, Edward Doisy and Paul Karrer

Answer 4

Determined the structure

Question 5

Vit K: Nobel prize

Answer 5

Dam for discovery and Doisy for chemical nature

Question 6

Vit K: Structure

Answer 6

Phylloquinone– 2-methyl-1-4-napthoquinone & isoprenoid side chain.

Question 7

Vit K: Plant biologically active form

Answer 7

phylloquinone- vitamin K1

Question 8

Vit K: Bacteria active forms

Answer 8

Menaquinone-4 and -7

Question 9

Vit K: Synthetic active form

Answer 9

Menadione- only water soluble

Question 10

Vit K: Fermented cheeses

Answer 10

Menaquinone-4

Question 11

Vit K: Fermented soy products

Answer 11

Menaquinone-7

Question 12

Vit K:Food Sources

Answer 12

Cabbage,. Pretty widely distributed around except for fruits* Deficiency is very uncommopn

Question 13

Vit K: Absorption

Answer 13

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.

Question 14

Vit K: Hepatic metabolism

Answer 14

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.

Question 15

Vit K: Transport and tissue uptake

Answer 15

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.

Question 16

Vit K: Storage and secretion.

Answer 16

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.

Question 17

Vit K: Excretion

Answer 17

Feces and urine.

Question 18

Vit K: Functions

Answer 18

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.

Question 19

Vit K: Blood clotting proteins

Answer 19

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.

Question 20

Vit K: Function of Gla residues

Answer 20

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.

Question 21

Vit K: Final steps in blood clotting

Answer 21

1. 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.

Question 22

Vit K: Vitamin K dependent clotting factors

Answer 22

IX, X, IXa, VIIa, Xa, VII, Prothrombin (factor II) and Thrombin (factor IIa).

Question 23

Vit K: Prothrombin time test

Answer 23

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.

Question 24

Vit K: Antagonists

Answer 24

Dicumarol. Warfarin (brand name= coumadin). Used as therapy to prevent thromboembolisms (such as stroke, myocardial infarction). Warfarin also used as rat poison. Anticoagulant.

Question 25

Vit K: Warfarin

Answer 25

Inhibits quinone reductase. So it cant go from quinone to dihydroquinone which is needed for gamma-glutamate carboxylate…

Question 26

Vit K: Diet and dicumarol drugs

Answer 26

Many patiens on dicumarol drugs are vitamin K depleted due to instructions to restrict intake– older recommendation to restrict Vit. K are outdated… In vitamin- K depleted patients small day-to-day changes in dietary intake may be important determinant of day-to-day variability in dicumarol dose-response. Key advice to patients on dicumarol drugs– maintain usual dietary pattern and report any planned changes in diet or multivitamin usage… do not need to avoid all the green veggies.

Question 27

Vit K: Dependent bone proteins

Answer 27

Two vitamin K-dependent proteins are present in bone, cartilage and dentine: osteocalcin (bone Gla protein) and Matrix Gla protein.

Question 28

Vit K: Osetocalcin

Answer 28

Secreted by osteoblasts during bone matrix formation. Comprises 15-20% of noncollagen protein in bone. Appears to function as a regulator of bone mineralization. Adheres to bone mineral hydrozyapatite. Has 3 Gla residues that bind calcium.

Question 29

Vit K: Matrix Gla Protein (MGP)

Answer 29

Associated with mobilization of bone calcium. In vitamin K deficiency, under-carboxylation of MGP increases calcification of atherosclerotic lesions.

Question 30

Vit K: Markers of deficiency

Answer 30

Proposed indicator of inadequate vitamin K. Undercaboxylated prothrombin liver. – Protein induced by vitamin K absence (PIVKA).. Undercarboxylated osetocalcin (ucOC)- bone

Question 31

Vit K: Deficiency

Answer 31

Uncommon in healthy adults. Seen in individuals with GI malabsorptive disorders. Newborns particulary at risk: food is limited to milk (low in vitamin K), stores are low because vitamin K does not efficiency cross placenta, Intestine is not yet populated with Vitamin K- synthesizing bacteria.

Question 32

Vit K: Defiency- Newborns

Answer 32

Infants born in US and Canada hospitals routinely receive 0.5 to 1 mp phylloquinone IM within 6 hours of birth. Hemorrhagic disease of newborn can affect infants up to 3-4 months of age: intracranial hemorrhage, CNS damage, Liver damage

Question 33

Vit K: AI

Answer 33

120 males. 90 females

Question 34

Vit K: Toxicity

Answer 34

No upper limit. Phylloquinone and menaquinone- nontoxic. Menadione can be toxic– liver damage. In infants: hemolytic anemia, hyperbilirubinemia, jaundice.