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nutr 302 > Vitamin K > Flashcards

Vitamin K Flashcards

1
Q

What are the 2 active forms of vitamin K?

A
  • phylloquinone (VitK1): natural form found in food
  • menaquinone (VitK2): made by intestinal bacteria
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2
Q

What is the active site of (active) VitK?

A

the ring structures

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3
Q

What is vitK soluble in?

A

fat soluble
* found in fats and oils in food

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4
Q

What is the main action of vitK

A

Post-translational carboxylation of proteins:
Gamma-carboxyl glutamic acid (Glu-COO-)
* Modifies Glutamic acid of calcium binding proteins by oxidixing it and adding another CO2 group giving it an extra negative charge which alloes Ca2+ to bind proteins

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5
Q

What are the Ca2+ binding proteins that vitK modifies important for?

A
  • blood clotting
  • bone formation
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6
Q

Describe the vitK cycle

A
  1. Vitamin K is activated through quinone reductase which requires NADPH
  2. activated vitamin hydroxyquinone is formed
  3. A protein containing glutamic acid is carboxylated via vitamin-K dependant carboxylase using the active vitK, O2 and CO2 such that Ca2+ can now bind and forms a vitamin K epoxide
  4. vitamin K epoxide is reduced back to vitamin K where it can be reused
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7
Q

What are the main proteins that are that are targeted by vitK?

A

Both cantain glutamic acid residues
* osteocalcin
* prothrombin (and other blood clotting factors)

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8
Q

Describe Warfarin

A

Drug used as anticoagulant for therapeutic purpose for people who were clotting too much and could stop regeneration of vitamin K by inhibiting action of vitamin K-epoxide reductase thereby reducing clotting ability of vessels
* Structural analog of vitamin K

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9
Q

What is required in order for glutamic acid residues on proteins to be modifed by vitK?

A
  • vitamin K
  • O2
  • CO2
  • NAD(P)H
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10
Q

Draw Vit K cycle

A
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11
Q

What is the main biological role of vitK?

A
  • needed for blood clotting
  • bone metabolism
  • some cardiovascular and neurological function
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12
Q

Role of vitamin K in blood clotting

A

Vitamin K is a part of making the zymogen blood clotting proteins
* The proteins prothrombin (FII), proconvertin (FVII), christmas factor (IX), stuart factor (FX) are made in liver as inactive zymogens and undergo post-translational modification via 𝛾-carboxylation of glutamic acid residues and vitK is a cofactor of the 𝛾-carboxylation. This allows Ca2+ to bind

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13
Q

Draw a diagram of VitK action in blood clotting

A
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14
Q

Where does vitK target in bone metabolism?

A
  • osteocalcin
  • matrix Gla protein (MGP)
  • Protein S
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15
Q

Describe osteocalcin

A

A small protein of 40-50 AAs synthesized by osteoblasts (induced by vitD) which contains hydroxyproline (dependant on vitC) and binds to hydroxyapatite crystals (Ca + P) in bone.
* Activity depends on carboxylation of glutamic acid
* Also found in kidney, lung and spleen

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16
Q

Describe MGP

A

matrix Gla protein - A protein that is expressed in developing bone prior to ossification and plays a role in organization. it also inhibits inappropriate calcification of epiphyseal (growth) plate
* Activity depends on carboxylation of glutamic acid; vitamin K2 dependant
* high affinity to bind Ca2+

17
Q

Describe protein S

A

Another Gla protein
* modulates cell proliferation

18
Q

VitK role in cardiovascular and neurological function

A
  • MGP activation by vitamin K may prevent premature calcification in cartilage and arterial vessels walls by inhibiting deposition of extra-cellular calcium matrix
  • Activation of the Gas6 protein (needed for neuronal development)
  • Important in sphingomyelin synthesis
19
Q

Absorption of vitamin K

A

Vitamin K absorbed in jejunum & is dependent on bile salts & lipids
* Transported in plasma in inner core of chylomicrons and LDL
* What is not absorbed will be excreted from feces in large quantities from bacterial sources; non excreted in urine

20
Q

Storage if Vitamin K

A

major storage site is the liver
* liver has limited capacity for long-term storage of Vit K
* phylloquinone (diet) is 10% of total liver stores of Vit K; menaquinones (microbiome) are the rest

21
Q

Excretion of Vitamin K

A

phylloquinone catabolized by liver whereby catabolic products are excreted partly in urine & partly in feces via bile
* appears from tracer studies that 60-70% of phylloquinone absorbed from each meal will be excreted

22
Q

Sources of VitK

A
  • Green leafy vegetables such as spinach, brocolli, turnip greens
  • Soybeans, beef, liver (low amounts phylloquinnone, higher in menaquinone)
  • Cooking oils such as canola, olive oil & soybean oil
  • Intestinal bacterial synthesis of vitamin K is sufficient to meet needs of the body
23
Q

Vitamin K DRIs for adults

A

90μg/d (female) - 120μg/d (male)
* this is available in normal diet
* No UL and toxicity is rare

24
Q

What is the most common disease with Vitamin K?

A
  • Hemorrhagic disease of the newborn
  • adults on antibiotic therapy known to interfere with vitamin K metabolism (N-methylthiotetrazole) since it kills the microbiome
25
Q

How can Vitamin K status be assessed?

A
  • Delayed prothrombine time (PT) - clinical
  • Phylloquinone serum levels
  • Assess undercarboxylated proteins - research
  • Elevated levels of protein induced vitamin K absence-II (PIVKA-II)
26
Q

What might cause vitamin K deficiency in adults?

A

The problem is typically not with intake but rather secondary causes such as GI tract issues and or drug induced (fat malabsorption, biliary obstruction, ileum resection, antibiotics)
* results in abnormal blood coagulation, so manifests bleeding, increased bruising, mucous membrane hemorrhave, post trauma internal bleeding

27
Q

Describe the process of fat malabsorption resulting in vitK deficiency

A
28
Q

Describe the vitamin K deficiency that is common in infants

A

There is very little transfer of vitK to the fetus and none is stored so at birth infants have low vitK status and low concentration of the vitK dependant clotting factor precursor proteins therefore more susceptible to vitK deficiency bleeding (VKDB). Infants also do not have a microbiome to make vitK.
* takes several weeks after birth to attain adults levels of vitK liver stores

29
Q

Where do infants start to get vitK from?

A
  • Newborns are dependant on breastmilk to supply vitK and delay may be risk factor for VKBD
  • babies routinely receive intramuscular or oral doses of Vit K as prophylactic measure against VKDB
30
Q

What is VKDB?

A

Vitamin K deficiency Bleeding

31
Q

What does the K stand for?

A

Koagulation

nutr 302 (20 decks)

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