Vitamin K: What we know about it

Vitamin K, Protein, Carboxylase, Effects

Vitamin K is a necessary participant in synthesis of several proteins that mediate both coagulation and anticoagulation. Vitamin K deficiency is manifest as a tendency to bleed excessively. Indeed, many commercially-available rodent poisons are compounds that interfere with vitamin K and kill by inducing lethal hemorrhage.

Physiologic Effects of Vitamin K

Vitamin K serves as an essential cofactor for a carboxylase that catalyzes carboxylation of glutamic acid residues on vitamin K-dependent proteins. The key vitamin K-dependent proteins include:

Coagulation proteins: factors II (prothrombin), VII, IX and X
Anticoagulation proteins: proteins C, S and Z
Others: bone proteins osteocalcin and matrix-Gla protein, and certain ribosomal proteins

These proteins have in common the requirement to be post-translationally modified by carboxylation of glutamic acid residues (forming gamma-carboxyglutamic acid) in order to become biologically active. Prothrombin, for example, has 10 glutamic acids in the amino-terminal region of the protein which are carboxylated. Without vitamin K, the carboxylation does not occur and the proteins that are synthesized are biologically inactive.

What essential function do gamma-carboxyglutamic acid residues endow upon a protein? There appear to be two major effects:

First, they enable the protein to bind to membrane surfaces. Much of blood clotting is a result of blood-clotting proteins assembling into a complex on the membranes of platelets and endothelial cells; within these complexes, the factors can efficiently contact one another to become activated and participate in clot formation. Additionally, calcium is necessary for the blood clotting reaction. The proposed mechanism involving carboxylation is that gamma-carboxyglutamic acid residues strongly chelate calcium, and positively-charged calcium forms ion bridges to negatively-charged phosphate head groups of membrane phospholipids.
Second, gamma-carboxyglutamic acid groups appear to participate in forming the necessary structure of such proteins by forming calcium-mediated intrachain interactions that link two gamma-carboxyglutamic acids to a calcium ion (similar to disulfide bridges, but much shorter).

Sources of Vitamin K

Vitamin K is found in a number of foods, including leafy greens, cauliflower and, if you consider it a food, liver. However, the chief source of vitamin K is synthesis by bacteria in the large intestine, and in most cases, absence of dietary vitamin K is not at all deleterious. Vitamin K is a fat-soluble vitamin and both dietary and microbial vitamin K are absorbed into intestinal lymph along with other lipids. The fetus obtains vitamin K from its mother by transplacental transfer.

The Vitamin K Cycle

As a cofactor to the carboxylase that generates gamma-carboxyglutamic acid, Vitamin K undergoes a cycle of oxidation and reduction that allows its reuse. The essential details of this cycle are:

Vitamin K (usually K1) is reduced to vitamin KH2.