Vitamin K Flashcards
Vitamin K produced by bacteria
Colonic bacteria provide a large source of menaquinones but it is not enough to meet our needs
Types of vitamin K found in diet
Phylloquinone - found in plants and oils
Menaquinones - some in animal products
Absorption of vitamin K
Phylloquinone is absorbed mainly in the jejunum
It requires normal fat digestion and absorption
Functions of Vitamin K
It is required for post translational modifications of specific proteins
-carboxylation of specific glutamic acid (GLU) residues to generate y-carboxyglutamate (GLA) residues– it becomes functional
Also essential for blood clotting and bone mineralization
What is the active form of vitamin K?
hydroquinone (KH2)
How is hydroquinone produced?
Through reductases that require dithiols or NADPH
What requires hydroquinone?
K-dependent enzymes in order for carboxylation to occur
-epoxide is generated
What does blood clotting require?
Requires that fibrinogen be converted to fibrin (active)
-Fibrin aggregates to form an insoluble polymer that is cross-linked with stabilizing factors to form a clot to stop bleeding
Blood - cells =
Plasma
Blood - cells - fibrinogen =
serum
What catalyzes the reaction to form fibrin?
The reaction of prothrombin to thrombin (active)
What two pathways convert pro-thrombin to thrombin?
Extrinsic (tissue factor exposed)
Intrinsic (collagen exposed)
Vitamin K dependent carboxylated proteins that are involved in blood clotting
Factor VII - extrinsic pathway
Factor IX - intrinsic pathway
Factor X - Stuart-prower factor; both pathways
Factor II - thrombin, both pathways
All require GLA residues and CA to interact with phospholipids
Vitamin K dependent anti-clotting factors
Protein C -associates with thrombomoudlin/calcium in the presense of thrombin & protein Ca
Protein S - interacts with Protein Ca and calcium to inactivate factors Va and VIIa
Protein X- unknowin function
What are anticoagulants?
Coumarin (in licorice and lavender)
It is used for people at risk for thrombosis and embolism
Causes huge problems in pregnant women (stillbirth, abortion, skeletal fractures)
Two Vitamin K dependent proteins in bone
Osteoclacin (bGP) - bone remodeling & Ca mobilization
Matrix GLA protein (MGP) - Ca mobilization and prevents calcification of cartilage
How is the synthesis of the two vitamin k dependent proteins stimulated
by 1,25-(OH)2D3 (calcitriol) and retinoic acid
Who is at risk for vitamin K deficiency?
-It is extremely unlikely in healthy individuals
-Populations at risk are:
GI malabsorptive disorders (biliary fistula, obstructive jaundice and liver disease)
Newborn infants - poor placental transfer and breast milk is low in vitamin K
Chronic antibody consumption
How is vitamin K assessed?
Plasma level of phylloquinone
Blood clotting times
Measurement of undercarboxylated proteins (prothrombin or osteocalcin)
What form of the vitamin do K-dependent enzymes require?
Hydroquinone
Carboxylation can then occur and epoxide is generated
