Vitamin K Flashcards
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
food sources K
K1 = plants
high, green veg
mid, veg and seed oils, legumes, coffee
low, fruit, dairy, meat, tea
3 assessments of Vit K status
- Static: plasma levels of phylloquinone, recent intake only
- Functional: prothrombin time: time for blood to clot (normal 11-14sec, over 25 sec means risk of hemorrhage)
- Functional: undercarboxylated prothrombin levels in plasma
K interactions with other nutrients
- A and E antagonize K
- Excesses interfere with absorption and metabolism
Vit K toxicity
No UL, menadione toxic in high doses, restricted supplements bc of wide use of coumadins
metab K
phylloquinone is metabolized and excreted mainly in feces
menaquinone degradation similar, side chain is shortened
(glucuronic acid conjugation)
why are mexican vanillas problematic
artificial vanillas made with coumarin (related to coumadin= blood thinner=inhibits vit K)
