vit K Flashcards
what type of vitamin is vit K
Fat soluble vitamin. Along with D, A and E
whys it called vit K
as its importance in blood clotting so vit K for koagulation
when was vit K discovered and who by
Between 1929 and 1935 Henrik Dam discovered a nutrient that had a vital role in blood clotting.
vit K was originally discovered as what kind of disease
haemorrhagic disease of chickens and cattle due to fat-free feed or dicoumarol presence.
what are the strictures of vit K
Two naturally occurring vitamers
- Phylloquinone (K1) - plants
- Menaquinones (K2) - animal sources & synthesized by intestinal bacteria
Synthetic compounds
- menadione
- menadiol diacetate
These are water soluble and can be metabolized to vit K1
what do synthetic vit K antagonists do
interfere with action of vit K by competing for binding sites at receptors so prevent clotting ability
what are examples of synthetic vit K antagonists and what do each of them do
Dicoumarol – excessive intakes impair blood clotting.
Warfarin – developed for clinical use as anticoagulant.
what are the functions of vit K
mainly for blood clotting and bone health
Involved in blood coagulation/ clotting – involved in cascade of reactions involving production of different proteins.
Role in bone proteins. Preventing osteoporosis
Possible role in cell signalling, brain lipid, regulation of calcium in the kidney. But more research is needed so focus on first 2 roles
Role mediated through action of both K1 and K2 acting as co-factor in conversion of protein bound glutamate residues to gamma carboxyglutamate (Gla) in a diverse group of proteins.
explain what vit K is needed as in blood coagulation
Needed as a Co-factor for the carboxylase enzyme that facilitates the synthesis of the unusual amino acid -carboxyglutamic acid (Gla).
what is Gla needed for formation of
Coagulation proteins (prevent bleeding): factors II (prothrombin), VII, IX & X
Anticoagulants: proteins C & S inhibit clotting process
what contain 4 - 6 Gla residues
Prothrombin and other proteins
what does Gla chelate and then permit the binding of
Gla chelates Ca ions and permits binding of blood clotting proteins to lipid membranes. So absence of Gla would cause impaired coagulation process
what does the coagulation/ clotting cascade do
converts blood from liquid to gel, and leads to fibrin formation
explain the full coagulation/ clotting cascade process
the intrinsic pathway occurs from clotting triggered by atherosclerotic plaque. vit K slowly produces thromboplastin
the extrinsic pathway occurs from clotting triggered by a cut finger. vit K fastly produces thromboplastin
Vit K produces thromboplastin which catalyses conversion of prothrombin to thrombin which converts soluble fibrinogen to insoluble strands or threads of fibrin, which is bound to platelets and hardens so forming clot or plug over wound.
Vit K also needed to give preprothrombin which has ability to bind to calcium ions which is important for clotting
explain how vit K is involved in bone formation
Gla present in bone matrix proteins osteocalcin (OC) & bone matrix Gla protein.
Treatment with warfarin or other anticoagulants in pregnancy has lead to foetal bone abnormalities due to impaired synthesis of OsteoCalcin.
OC thought to be involved in limitation of bone growth.
does vit K increase or decrease bone mineral density in osteoporosis
increase
does vit K increase or decrease fracture rates
decrease
vit K works____with vit_____on _____
synergistically (combined affect is greater than sum of individual affect) with vit D on bone density
vit K has what type of influence on calcium balance
positive
what are sources of K1
Phylloquinone (K1): green leafy vegetables ( as has role in photosynthesis) & vegetable oils
what are sources of K2
Menaquinones (K2): fermented food like cheese and yoghurt
what are sources of Menadione & menadiol diacetate:
synthetic compounds that can be metabolised to phylloquinone
what the impact of food composition data being limited
limits research on role in health.
why is further work needed on storage and bioavailability of vit K
Storage - UV light may cause reduction.
Bioavailability - absorption from boiled spinach improved with addition of butter. So depends on what food is consumed with
what are some high and some low Sources of phylloquinone
Cabbage and broccoli are richest sources also rape seed oil and olive oil is, lots in lettuice .
Theres very little in eggs
explain some Sources of menaquinones
More restricted distribution in diet than K1
Found in Foods with a bacterial fermentation stage. Yeasts don’t synethsise menaquinones
Found in Animal livers and fermented foods such as cheese.
Found In fermented soya beans in Japanese natto (MK-7). MK= menaquinone, 7= number of side chains
MK-4 synthesised in animal tissues from menadione.
Intestinal bacterial synthesis many Mk with diff what
lengths of side chain
MK-10 and MK-11 by Bacteroides
MK-8 by Enterobacter
MK-7 by Veillonella
give a summary of how vit K goes from sources to destination
Vit K is absorbed with fat in small intestine and the intestinal cells package vit K in chylomicrones and export them to lymphatic system, which is part of circulatory system and it carries a clear fluid of lymph (recycled blood plasma) towards the heart. Vit K is stored in liver and necessary for many steps in blood clotting and needed for synthesis of osteocalcin in bone.
Intestinal cells package vit K in what, and transport them where
chylomicrons and transport to lymphatic system.
Chylomicron remnants transport vit K to liver. Liver is a significant storage site (10% K1 and 90% K2 is stored).
vit K is exported in liver in what
very low density lipoprotein (VLDL).
Plasma concentration of vit K depends on what
total plasma lipids present that are being carried by the lipoproteins.
what percentage of dietary K1 is lost from body in excretion (urine or bile)
60-70%
what does the dietary K1 loss from body in excretion suggest
high turnover rate and need for constant replenishment.
how much Phylloquinone is absorbed and whats it incorporated into
80% absorbed and incorporated into chylomicrons
how much Menaquinones are absorbed from large intestine
a limited extent
Menadione is absorbed largely into what system and what does it undergo
into hepatic portal system and undergoes alkylation in liver to yield menaquinone-4.
Released with K1 & other K2 in VLDL.
why is there such few studies for vit K requirements
requirements due to difficulties inducing deficiency through dietary deprivation
DRV for vit K are based on
determination of clotting time and measurement of prothrombin & preprothrombin.
what are the safe intakes of vit K for infants
10 μg/day. Babies to receive prophylactic K1 at birth.
whats the safe intakes of vit K for adults
1μg/kg/d is safe and adequate (60-80 μg/day).
explain lack of vit K deficiencies
Bleeding disorder - low plasma prothrombin activity.
Abnormal precursor of prothrombin released into circulation: preprothrombin - contains little/no γ-carboxyglutamate.
Preprothrombin cannot chelate calcium ions or bind to phospholipid membranes, so unable to initiate blood clotting.
Suboptimal status linked with osteoporosis.
whos at risk of vit K deficiency
Newborns given vit K to prevent haemorrhagic disease of the newborn (now known as vit K deficiency bleeding in infancy).
Those on anti-coagulant drugs e.g. warfarin & dicoumarol.
can toxicity occur from high intakes of phylloquinone or menaquinone
no evidence
Menadione given to babies has been associated with what
haemolytic anaemia and jaundice. Prophylactic vitamin K given at birth should be phylloquinone.
high vit K intakes can overcome affects of what
warfarin and other anticoagulants.
why cant a safe upper limit be established
insufficient data
