Vitamin K

Question 1

What are the 2 active forms of vitamin K?

Answer 1

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

Question 2

What is the active site of (active) VitK?

Answer 2

the ring structures

Question 3

What is vitK soluble in?

Answer 3

fat soluble
* found in fats and oils in food

Question 4

What is the main action of vitK

Answer 4

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

Question 5

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

Answer 5

• blood clotting
• bone formation

Question 6

Describe the vitK cycle

Answer 6

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

Question 7

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

Answer 7

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

Question 8

Describe Warfarin

Answer 8

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

Question 9

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

Answer 9

• vitamin K
• O2
• CO2
• NAD(P)H

Question 10

Draw Vit K cycle

Answer 10

Question 11

What is the main biological role of vitK?

Answer 11

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

Question 12

Role of vitamin K in blood clotting

Answer 12

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

Question 13

Draw a diagram of VitK action in blood clotting

Answer 13

Question 14

Where does vitK target in bone metabolism?

Answer 14

• osteocalcin
• matrix Gla protein (MGP)
• Protein S

Question 15

Describe osteocalcin

Answer 15

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

Question 16

Describe MGP

Answer 16

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+

Question 17

Describe protein S

Answer 17

Another Gla protein
* modulates cell proliferation

Question 18

VitK role in cardiovascular and neurological function

Answer 18

• 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

Question 19

Absorption of vitamin K

Answer 19

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

Question 20

Storage if Vitamin K

Answer 20

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

Question 21

Excretion of Vitamin K

Answer 21

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

Question 22

Sources of VitK

Answer 22

• 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

Question 23

Vitamin K DRIs for adults

Answer 23

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

Question 24

What is the most common disease with Vitamin K?

Answer 24

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

Question 25

How can Vitamin K status be assessed?

Answer 25

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

Question 26

What might cause vitamin K deficiency in adults?

Answer 26

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

Question 27

Describe the process of fat malabsorption resulting in vitK deficiency

Answer 27

Question 28

Describe the vitamin K deficiency that is common in infants

Answer 28

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

Question 29

Where do infants start to get vitK from?

Answer 29

* 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

Question 30

What is VKDB?

Answer 30

Vitamin K deficiency Bleeding

Question 31

What does the K stand for?

Answer 31

Koagulation