Vitamin K Flashcards
Vitamin K sources
o Phylloquinone (formerly K1) • Leafy green vegetables • Legumes • Some plant oils: soy, canola, cottonseed, olive o Menaquinones (MK) (formerly K2) • Bacterial synthesis in digestive tract • Liver, meat, butter, egg yolk • Fermented cheeses and soy products (natto) o Menadione (formerly K3) • Synthetic form • Converted to MK-4 in vivo
Vitamin K stability
o Destroyed by exposure to light and heat
Vitamin K absorption
o Absorption occurs as part of micelles
o Enhanced with the presence of dietary fats, bile salts, and pancreatic juices
o Phylloquinone is absorbed in the small intestine, particularly the jejunum
o Menaquinones
• Synthesized by bacteria in the lower digestive tract and absorbed by passive diffusion from ileum and colon
• Absorption varies from person to person
• Absorbed better than phylloquinone
Vitamin K transport
o Within the enterocyte vitamin K is incorporated into chylomicrons for transport to tissues and then the chylomicron remnant deliver residual vitamin K to the liver
o Vitamin K is incorporated into VLDL and ultimately carried to extra hepatic tissues in LDL and HDL
Vitamin K storage
o Stored primarily in the liver
Vitamin K functions
o The primary function of vitamin K is to serve as the cofactor for a carboxylase enzyme that catalyzes the γ-carboxylation of glutamic acid residues on specific proteins
o This conversion of glutamic acid to γ-carboxyglutamate activates these proteins by creating effective binding sites on the proteins
Vitamin K functions necessary for what?
• Blood clotting
• γ-carboxylation of glutamate residues is required for the activation of 6 proteins that regulate the coagulation of blood
• 4 clotting factors: II (prothrombin), VII, IX, & X
• 2 anticoagulant proteins: proteins C & S
• Bone mineralization
• 2 vitamin K-dependent proteins have been identified in bone, cartilage and dentine
o Osteocalcin
• Stimulated by 1,25(OH)2D3
• Secreted by osteoblasts during bone matrix formation
• Activated osteocalcin facilitates the binding of calcium ions in the hydroxyapatite lattice
o Matrix Gla protein (MGP)
• Stimulated by 1,25(OH)2D3
• Plays a role in bone mineralization
• May also prevent arterial calcification
• Apoptosis
Vitamin K excretion
o Metabolites excreted primarily in the feces via the bile
o Phylloquinone are degraded much slower than menaquinones
Vitamin K deficiency symptoms
o Symptoms
• Hemorrhage due to prolonged prothrombin time
o Subclinical vitamin K deficiency
• May be associated with (but evidence is not definitive)
• Decreased bone mineral density → increased fracture rates
• Development of arterial calcification
Vitamin K increased risk of deficiency
- Newborns
- Young adults have a mean vitamin K intake of only 80 mcg/d
- Chronic antibiotic use
- Fat malabsorptive disorders
Vitamin K clinical indications
o Osteoporosis
o Atherosclerosis
o Hemorrhagic disease of the newborn
Vitamin K preparations
o Phylloquinone is the most widely used form
o Menaquinones: MK-4 and MK-7
Vitamin K toxicity
o Phylloquinone and menaquinones
• No symptoms of toxicity with ingestion of large amounts
• No UL has been established
• Some case reports of adverse effects from parenteral administration
o Menadione
• Hemolytic anemia and hyperbilirubinemia
o Caution with patient taking coumadin (Warfarin)
• Coumadin competitively inhibits vitamin K dependant activation of coagulation factors II, VII, IX, and X
• Increasing vitamin K intake inhibits the action of coumadin and vice versa
• Therefore patients taking coumadin must keep dietary vitamin K consistent
• However, studies have shown that taking 100-150 mcg/d of phyloquinone resulted in fewer fluctuations in INR
Vitamin K nutrient interactions
o Vitamin A
• Vitamin A toxicity has been associated with hypoprothrombinemia, inhibition of vitamin K absorption, synthesis by intestinal bacteria, and direct interference with vitamin K activity in the liver
o Vitamin E: 2 metabolites of vitamin E have anti-vitamin K activity
Vitamin K assessment of status
o Plasma or serum phylloquinone only reflects intake within the past 24 hours
o INR or prothrombin time
• Relatively insensitive as plasma prothrombin concentrations must decrease significantly to produce any effects on INR or prothrombin time
o Undercarboxylated vitamin K-dependent proteins
• Vitamin K deficiency results in the production of under or partially carboxylated proteins
• 1,000 times more sensitive than prothrombin time
