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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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