Vitamin K

[KB2:p206-207]

Function

Allows production of certain proteins

• Clotting proteins that are vitamin-K dependent
  --> Factors 2,7,9,10, protein C and protein S
• Bone protein
  * e.g. osteocalcin

Mechanism of action

Vitamin K is a cofactor for the enzyme (carboxylase) that catalyzes the conversion of glutamic acid residues to gamma-carboxyglutamic acid residues
* Vitamin K is oxidised during this reaction
* After this reaction, vitamin K needs to be reduced to become active cofactor again

Vitamin K allows for donation of a COOH group
--> Allows the clotting factor to bind to PF3 or TPL by a Ca2+ bridge

NB:

• The conversion is an example of post-translational modification

Vitamin K intake

• Dietary vitamin K
  * Absorbed from small intestine
  * Fat-soluble, thus require bile salt
• Some vitamin K is produced by bacteria in terminal ileum and large amounts are produced in colon
  * But only vitamin K produced in terminal ileum is absorbed
  * Vitamin K produced from bacteria in colon is not absorbed

NB:

• Vitamin K enters the circulation in chylomicrons in the lymphatics

Vitamin K in newborn

Newborn infants are vitamin K deficient because

• Vitamin K does not cross the placenta in sufficient amount
• Bacterial production of vitamin K in newborn does not occur in the first week of life
• Dietary intake of vitamin K is poor
  * Breast milk has low levels of vitamin K

As a result
--> Haemorrhagic disease of the newborn

NB:

• Phenytoin taken by mothers during pregnancy concentrates in the foetal liver
  --> Inhibits the action of vitamin K

Coumarin

Coumarin derivatives (e.g. dicumarol and warfarin)
--> Inhibits the reduction of vitamin K after it was oxidised during the conversion
--> Vitamin K cannot be recycled back into active co-factor

Vitamin K injection

Vitamin K injection is used to reverse the effect of warfarin
* Also come in tablets

• If anticoagulation with warfarin is needed afterwards
  --> 1-2mg of vitamin K (IV)
  * 8-12 hours are required for the effect to set in 
• If anticoagulation with warfarin is not needed
  --> 10mg of vitamin K
  * It is a very large dose
  * Warfarinisation is difficult after 10mg of vitamin K
• Reversal of warfarin with vitamin K takes time
• Fresh frozen plasma is used to quickly replace the clotting factors