ansc314 - vitamin E & K

vitamin E

• abundant in vegetable oil, nuts & seeds

• tocopherol

  • tokos - childbirth/offspring

  • pherein - to bring forth

  • ol - alcohol

• crucial to break lipid peroxidation & protection cell membrane

vitamin E structure

tocopherols & tocotrienols (active forms of vit E)

• group of chromanol compounds

  • play crucial role in breaking lipid peroxidation & protecting cell membrane function

tocopherols

• a form of tocochromanols

• 4 forms: 𝛼, ꞵ, γ, δ

  • diff in # of position of methyl groups on chromanol head group

tocochromanols

• made of:

  • head - chromanol ring system (antioxidant portion)

  • tail - hydrophobic prenyl side chain

• 2 groups

  • tocopherols & tocotrienols

    • differ in saturation

vitamin E functions

• antioxidant (most important)

  • stop lipid peroxidation as molecular oxidant

  • cooperate w/ enzymatic antioxidants

• immune enhancer

  • adequate vit E status plays an important role immune function

  • cows w/ depleted vit E status have impaired neutrophil function

lipid peroxidation

Lipid peroxidation

• free radicals oxidize lipid membranes, producing lipid radicals & and H₂O

• aerobic environment (L)

  • can oxidize 1 free oxygen molecule, giving rise to a lipid peroxyl radical (LOO•)

• highly reactive continue to oxidize PUFAs to produce lipid hydroperoxide + additional

• Lipid peroxidation chain reaction continues in the cell membrane leading to cellular dysfunction

radical

• unsaturated (more DB) FA ↑ prone to oxidation (BAD)

• lipids prone to oxidation

  • vit E helps prevent oxidization of FA

free radical oxidation

• vit E donates e^- to protect cell membranes

  • reduces free radicals that dmg FA in phospholipid bilayers

• free radials have unpaired e^- → unstable

  • dmg (oxidize) FA in phospho. bilayer

• vit E reduce free rad → stable → no dmg

vitamin E pathway

vit E 1st line of defense

1. vit E reduce free radical → stable

2. vit C reduce oxidized vit E

3. glutathione peroxidases reduce vit C

• all so vit E can keep reducing phospholipid bilayer

  • glutathione peroxidase

  • superoxide dismutase

• GSSG – glutathione

• GSH – reduced glutathione

vitamin E & selenium

• selenium spares vit E & delays onset of deficiency symptoms

• vit E protects against / delays onset of several forms of selenium deficiency symptoms

• ↑ dietary PUFA ↑ vit E requirements

  • ↑ PUFA → ↑ C=C bonds attacked by OH radical

• vit E & selenium protects against FA tissue peroxidation

  • vit E 1st line of defense in cellular & subcellular membranes

  • selenium 2nd line of defense as part of glutathione peroxidase

vitamin E sources

• wheat germ (most concentrated)

• almonds

• olive & sunflower oils (𝛼-tocopherol)

• soybean & corn oils: (gama γ - tocopherol

• gras lipid fraction

• synthetic forms: all-rac-𝛼-TOH

  • DL mixture (rac - racemic)

    • ½ potency of natural d-𝛼-TOH

natural vit E

vitamin E absorption, transport, storage

• high affinity receptor for LDL demonstrated to function as mechanism of delivery of vit E → cells

vitamin E roles

• coronary heart disease

  • vit E inhibits platelet aggregation → reduce risk of CHD

• disease resistance

  • vit E & selenium (glutathione peroxidase) protect leukocytes & macrophages during phagocytosis of bacteria

    • chicks: large doses of vit E protect against E. coli infections

    • pigs: vit E ↑ resistance to dysentery

    • calves: 125 IU of vit E daily maximizes their immune response

vitamin E requirements

• humans - fairly low

• animals

  • 1 mg vit E per 1 g of polyunsaturated FA in diet

    • adding essential FA ↑ need for vit E supplementation

  • vit E requirements ↑ if PUFA are ↑ & vice versa

vitamin deficiency symptoms

• stiff lamb disease - nutritional myopathy in sheep & cattle (antioxidant role)

• cardiac disease in young

• encephalomalacia (crazy chick disease)

  • affects 204 wk-old chicks, severe muscle incoordination, vascular lesions in brain

• RBC fragility - prone to hemolysis

• erythrocyte destruction

• testicular degeneration in most male animals

• impaired fetal development → intrauterine death

encephalomalacia

softening of the brain

stiff lamb disease

most common vit E deficiency symptom

• nutritional muscular dystrophy

nutritional muscular dystrophy

disease caused by deficiency of selenium & vit E in dietary intake

• soils that contain ↓ lvl selenium produce forages & grains are deficient in selenium

vitamin K

• fat soluble vitamin

• stable to heat, but oxidized by light & UV radiation

  • name derived “Koagulation factor” Danish

vitamin K forms

• phylloquinone

• menaquinone

• menadione

phylloquinone

vitamin K1

• synthesized by plants

menaquinone

vitamin K2

• synthesized by gut/rumen

• microbes (bacteria-protozoa)

  • soluble by cutting it off

menadione

vitamin K3

• synthetic form

  • no hydrophobic side chain

• relatively water soluble & ↑ efficiently absorbed on ↓ diets

  • body can’t store it → need ↑ of it

• make ↑ water soluble to be ↑ easily absorbed

  • fat soluble is going to just be stored & long process to absorb it

vitamin K sources

• rumen bacteria

• ↓ gut bacteria

• alfalfa

• kale

• cauliflower

• green tea

• beef lier

• green, leafy veggies

vitamin K absorption, transport, storage

vit K blood clotting

vit K blood clotting

blood clotting pathway

carboxylation of glutamyl residues in prothrombin allows binding Ca+ for further conversion → thrombin

• vit K is cofactor for carboxylase to add CO₂ on 1 AA on 1 protein (glutamic acid)

(γ) gama-carboxyglutamate

vit K → prothrombin → thrombin

• vit K activates prothrombin

antagonists

anticoagulants

• inhibitors of blood clotting system

vitamin K deficiency

• poor blood clotting & anemia

• hemorrhagic disease of newborn

• uncommon in humans and animals

• antagonists

  • warfarin

  • dicoumarol

    • block Vit K-dep carboxylase reaction

story line: warfarin

Warfarin

• used to prevent & treat deep-vein thrombosis & pulmonary embolism to prevent stroke in patients who have atrial fibrillation, valvular heart disease, or a prosthetic heart valve

antagonism

• 1920s

  • Sweet Clover Disease (moldy clover)

  • Death by internal bleeding

• 1940

  • Active chemical isolated from blood

    • Coumarin → Dicoumarol (mold)

  • Patent to WI Alumni Research Foundation

• 1945

  • Wisconsin Alumni Research Foundation (WARF) funded development of rat poison

  • Warfarin (coumarin derivative)

• 1950’s

  • Developed to prevent thrombosis

  • Given to Dwight D. Eisenhower, 1955

  • Dose affected by vitamin K levels