Vitamin K ( anti-hemorrhagic vitamin )

- Is Required for Synthesis of Blood Clotting Proteins.

- Antagonists of vitamin K are used to reduce blood coagulation in patients at risk of thrombosis; the most
widely used is warfarin.

Three compounds have the biological activity of vitamin K (Figure 44–7):

1- phylloquinone, the normal dietary source, found in green vegetables;

2- menaquinones, synthesized by intestinal bacteria, with differing lengths of side-chain

3- menadione and menadiol diacetate, synthetic compounds that can be metabolized to

phylloquinone.

N.B. Menaquinones are absorbed to some extent, but it is not clear to what extent they are biologically active as it is
possible to induce signs of vitamin K deficiency simply by feeding a phylloquinone-deficient diet, without inhibiting intestinal
bacterial action.

- Role of Vitamin K in blood clotting :

1- Vitamin K is the Coenzyme for Carboxylation of Glutamate in Postsynthetic Modification
….of Calcium-Binding Proteins :

Vitamin K is the cofactor for the carboxylation of glutamate

residues in the post-synthetic modification of proteins to
form gamma-carboxyglutamate (Gla)

- First, Vitamin K Quinone is reduced to hydroquinone by

activity of enzyme quinine reductase that requires either
diathiol or NADPH .

- then, Vitamin K hydroquinone is oxidized to the

Vitamin K epoxide, which activates a glutamate residue in
the protein substrate to a carbanion, which reacts
nonenzymically with carbon dioxide to form gamma-
carboxyglutamate.

Vitamin K epoxide is reduced to the quinone by epoxide

reductase, and the quinone is reduced to the active
hydroquinone by quinone reductase.

N.B. In the presence of warfarin, vitamin K epoxide cannot be reduced,

but accumulates and is excreted

N.B.2 A high dose of vitamin K is the antidote to an overdose of warfarin.

Prothrombin(Factor II) and several other proteins of the blood clotting system (Factors VII, IX, and X, and proteins C and S)
contain glutmate residues, carboxylation of these glutamic acid residues into gamma-carboxyglutamate converts the molecule
into active thrombin (carboxylation occur also to the other factors and activate them).

gamma-Carboxyglutamate chelates calcium ions, and so allows the binding of the blood clotting proteins to membranes.

In vitamin K deficiency, or in the presence of warfarin, an abnormal precursor of prothrombin (preprothrombin) containing
little or no -carboxyglutamate, and incapable of chelating calcium, is released into the circulation.

For reading: prothrombin is a protein formed in the liver as inactive form called prothrombin precursor. It contains 10
glutamic acid residues .