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Vitamin K
Micronutrients HNS 7211
Prof. Kathleen Axen Spring 2014
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Forms of Vitamin K
Phylloquinones K1
green plants
Menaquinones
K2
animal sources
bacterial synthesis, GI tract
Menadione K3
synthetic
must be converted to K2 in liver in order to be active
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1,4-Napthoquinone
(core of the structure)
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Phylloquinone
2 methyl 1,4 napthoquinone 3 repeating units (single bonds)in side chain
Bacteria in gut can remove side chain
Resulting menadione is then converted tomenaquinone-4 (MK4) in tissues
~20% catabolized and excreted/day
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Menaquinone
Double bonds in repeating side chain MK4 has 4 sets of side chain units
concentrated in brain
Synthesized by GI bacteria
Human liver: K1:K2::1:10
MK 4 and 5 most active, MK7 high in legumes
MK4
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Menadione
synthetic
Water-soluble salts in supplements
Converted to MK4 in liver
Can produce toxicity: liver damage
Unstable in UV, alkali; degraded faster than K
or MK
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standard
Max activity
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Absorption and Excretion
Requires bile
K1-active transport in proximal SI
K2 & K3 passive diffusion
Incorporated into lipoprotein particles
Go to liver in Chylomicrons (lymph first)
VLDLLDL, HDL transport it to tissues
Liver storage
Poor placental transport
Excretion
via bile (feces); coprophagia provides vitamin
water-soluble urinary metabolites
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Coenzyme form
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Coenzyme
form: KH2
What does vitamin K do?
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Vitamin K-dependent gamma-
carboxylation
Post-translational modification of proteins
Acts on glutamic acid residues (9-12 sites) of
the peptide chain
Microsomal (ER bound)
Formation of GLA proteins
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Coenzyme
form: KH2
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KH2
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Gene-nutrient interactions
Mutations (Single Nucleotide Polymorphisms)
observed in population for:
Vit K gamma glutamyl carboxylase
Vit K epoxide reductase (recycles vitamin)
Vit K quinone reductase (forms coenzyme)
Warfarin resistance
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Clotting Factors
Synthesized in liver
Undergo vit K dependent gamma
carboxylation (GLA proteins) in liver
Can bind to Ca 2+
Activated in plasma as needed
Cascade activation Self-limiting
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soluble
insoluble
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fibrinolytic
*
*GLA proteins C
and S limit the
clotting cascade
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Some other GLA proteins
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Some other GLA proteins
Osteocalcin
(bone) affects bone mineralization? Influences bonemicrostructure?
increases adipocyte tissue development
Matrix GLA protein (MGP)
chondrocytes, osteoblasts vascular smooth muscle
Inhibits calcification of vessels( in MGP ko)
Gas6 Growth arrest gene 6 --brain
Increases growth, migration, cell survival,
myelination (low in Alzheimers)
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Bone
Some studies show vit K supplementation todecrease bone loss and/or fractures
Osteocalcin produced by osteoblasts(transcription and translation regulated bycalcitriol)a GLA protein.
Effect on bone architecture?
Bone GLA-rich Protein (GRP) involved?
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Other vit K effects
Anti-inflammatory effects through decreasedexpression of IL-6
Regulation of adipose tissue development,prevention of insulin resistance
Dietary requirements may differ for the variousfunctions of vit K
DRI 90-120 micrograms
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Warfarin
aka coumadin
Structurally similar to vit K
Competitive inhibitor
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Effect of Warfarin during pregnancy
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Vitamin K deficiency
Newborns hemorrhagic disease
Sterile GI tract, poor placental transport
Intracranial hemorrhage
1 mg vit k given im at birth Chronic lipid malabsorption
cystic fibrosis
Obstructive jaundice (no bile) Ileitis
Chronic antibiotics, excess coumarin therapy
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Indices of deficiency (biomarkers)
Des--carboxyglutamyl prothrombin
plasma prothrombin
clotting time (excess bleeding)
other GLA proteins
% uncOC is sensitive biomarker of vitK deficiency
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