Vitamin K

Question 1

Vitamin K Background

Answer 1

• Discovered when chickens bleed from low lipid diet
  
  • Treat with lipid extract of green plant/putrid fishmeal
• K1-alfalfa; K2-fish-meal
• Need vitamin K cycle to make sure never run out
  
  • Can’t rely on liver stores

Question 2

Vitamin K Structures

Answer 2

• 3 substituted, 2-methyl, 1-4 napthoquinone
• K1: phyloquinone
  
  • In liver
  • Cofator driving clotting
  • Green leafy
  • 2’3’ dihydro-junk food
• K2: menaquinone (MK1-13)
  
  • MK-4: food and formed in body by reacting K3 with geranylgeranyldiphosphate
  • MK-7: fermented food
  • MK-8-13: gut bacteria
• K3: Menadione “provitamin”
  
  • Lack side chain for activity
  • Converted to MK-4 with geranylgeranyldiphosphate

Question 3

Vitamin K Cycle

Answer 3

• Quinone from diet reduced to hydroquinone
• Hydroquinone→VitK Epoxide with GGCX (gamma-glutamyl carboxylase)
  
  • Glu to Gla (gamma-carboxyglutamic acid)
  • Inhibited by VitE
• VitK Epoxide→Hydroquinone
  
  • VKORC1 (Vitamin K epoxide redutase)
  • warfarin target
    
    • Inhibit 2, 5, 7, 9
• Ca²⁺ bind to Gla at N-terminus of vitK-dependent protin, conformational change, Gla protein anchor to membrane

Question 4

Vitamin K Metabolism

Answer 4

• omega hydroxylation
  
  • CYP4F2 and 4F11
• Subsequent beta-oxidation
• CH₃→CH₂OH→CO₂H→COSCoA
• Sulfate and glucoronide of chain shortened K excreted in bile and urine

Question 5

Vitamin K deficiency

Answer 5

• Hemorrhage
  
  • chronic lack of greens/long term antibio
• Equal K1/K2 contribution?
  
  • No because of poor bioavailability of K2 in lower gut
• Vit K assesed with PIVKA-II test measuring decarboxy-prothrombin with ELISA test

Question 6

Vitamin K uses: General (3)

Answer 6

• Coagulation
• Bone Health
• Prevention of vascular calcification

Question 7

Vitamin K: Use for Coagulation

Answer 7

• INR>9, no bleed; K1 oral 2.5-5mg
• INR>20, serious bleed; 10mg K1 slow iv and fresh plasma
• K1 at birth (IM 0.5-1mg)
  
  • Placenta=poor transfer
  • Breast milk low (2.5µg/L; cow 5000µg/L)
  • Gut sterile

Question 8

Vitamin K: Use for Bone Health

Answer 8

• gamma-carboxylation of osteocalcin for bone deposition
• 25 mg/d for 2 years decreased hip fracture, studies inconclusive about benefit

Question 9

Vitamin K: Use for preventionof vascular calcification

Answer 9

• gamma-carboxylation of MGP (matrix Gla protein), body natural calcification inhibitor
  
  • Role for dialysis patient?

Question 10

VitK source

Answer 10

• Green leafy
• 1000µg/cup

Question 11

Vitamin K Dose

Answer 11

• DV=80 µg
• UL=none
• Adequate Intake levels by IoM are 90-120 µg/day

Question 12

Vitamin K Toxicity

Answer 12

• allergic reaction to IV

Question 13

Vitamin K: Consumer Counseling

Answer 13

• For clotting and bone health
• Diet with leafy veggies can supply needs; amount in multivites assures good intake
• warfarin=steady vitK intake