Vitamin K Flashcards
(30 cards)
History/discovery, named after
- Named after Danish word “koagulation” (coagulation)
- Discovered by Henrik Dam in 1920s
- Edward Doisy isolated and synthesized in 1932
- Nobel prize in medicine awards to Dam and Doisy in 1941
forms of vit K
K1: phylloquinone
K2: menaquinone
MK-4: menaquinone with different isoprenoid units
only dietary source of K
phylloquinone, plant foods (green leafy, seed oils)
how do we get MK-4
synthesized in body from K1
what are menaquinones
made by gut bacteria and found in fermented foods
Phylloquinone metab steps
phylloquinone - menadione (K3) - menadiol = MK-4
K3
menadione
drug/synthetic form
animal feed and pet food industry
Vit K absorption
K1 absorbed from proximal small intestine
incorporated into micelle
passive diffusion through BBM
HIGH TURNOVER LITTLE STORAGE
how much K1 vs K2 absorbed
50% K1 (diet), 50% K2 (gut bacteria)
transport of Vit K
via chylomicrons and VLDLs
where is K stored
cell membranes of tissues
functions of Vit K
- Blood clotting
- Bone mineralization
- Supports CV health (prevents calcification of arteries, activates matrix Gla protein (MGP), which is a protein that inhibits calcification)
- Cofactor in synthesis if certain calcium-binding proteins
o Post-translational modification - 2 systems require Vit K-dependent proteins: bone and blood
K and glutamate
- Adds carboxy group to amino acid glutamate (Glu) -> Gla + CO2+ KH2 ACTIVE FORM -> carboxy-glutamic acid (can now bind Ca+2)
blood coagulation factors
2, 7, 9, 10
coagulation process
2= prothrombin
10 -> prothrombin cleaves -> thrombin
fibrinogen - thrombin - fibrin - factor 13active - clot
synthesis of prothrombin
- Prothrombin circulates in plasma
o Inactive but quickly converted to thrombin (active) - Made in liver (needs vitamin K as cofactor)
o In pre-prothrombin, Glu residues are changed to gamma-carboxy glutamic acid - Gla allows prothrombin to bind Calcium to create thrombin
Vit K cycle
- KH2 (dihydroquinone) + pre-prothrombin Glu + CO2 (gamma-glutamyl carboxylase) = prothrombin Gla
- CAN NOW BIND TO CALCIUM
- Convert back to KH2 for cycle to continue
- Vitamin K 2,3-epoxide + epoxide reductase = Vitamin K quinone
- *anticoagulant (warfarin) inhibit epoxide reductase - Reduced by dithiol
- = Vitamin K quinone
- Vitamin K quinone + quinone reductase + NADPH (reduce) = dihydroquinone KH2
- *anticoagulant (warfarin) block quinone reductase
simplified K cycle
- Diet intake, K into body
- Active form KH2
- Preprothrombin with Glu prothrombin with Gla
- K-epoxide
- K
- Repeat
warfarin inhibits what in K cycle
prevent/slow KH2 reforming
- Diet intake, K into body
- BLOCKED
- Active form KH2
- Preprothrombin with Glu prothrombin with Gla
- K-epoxide
- BLOCKED
- K
Vit K and bone formation
- Bone synthesis requires Gla proteins for mineralization
- Osteocalcin (OC): matrix Gla protein (MGP)
o Prevent calcification of soft tissues + vessels - Role of OC unclear, presumed for binding calcium during bone formation
MK-4 functions
carboxylation
Maybe:
brain function, sphingolipid metabolism, reduce inflam CVD osteoporosis
Primary deficiency K
Primary: diet inadequate
- Not seen in Vit K bc bacteria make it
- Blocking bacteria (antibiotics), inadequate diet, would lead to deficiency
- Blocking fat absorption blocks K from diet and bacterial synthesis
o Easy bleeding and bruising
Secondary Deficiency
Secondary: another reason for deficiency, not caused by diet
- Lack of bacteria
o Antibiotics that block K synthesis (if diet is also low in K)
o Newborns: sterile gut, low in breastmilk, born inn sterile environment = K shot
- Fat malabsorption: OLESTRA, celiac, crohn’s, cycstic fibrosis
- Vitamin E excess
- Coumadin drugs: intentional Gla inhibition -> prevent thrombosis (patients at risk of clot disorders)
K DRI
NO, only AI
19-50: M = 120mcg, F = 90mcg
