Vitamin K helps to regulate the process of blood coagulation by assisting in the conversion
certain coagulation factors into their mature forms.
Without vitamin K, our bodies would be unable to control clot formation.
Imagine being unable to form blood clots effectively--that would mean that we would lose all of our blood
volume from something as simple as a pinprick!
To prevent this extreme scenario - vitamin K must be ingested, metabolized, and utilized
to create mature coagulation factors.
Now, to understand the regulation of clot formation, we first need to talk briefly about
hemostasis--hemo referring to blood, and stasis meaning to halt or stop.
Hemostasis is divided into two phases: primary and secondary hemostasis.
Primary hemostasis involves the formation of a platelet plug around the site of an injured
blood vessel, and secondary hemostasis reinforces the platelet plug with the creation of protein
mesh called fibrin.
To get to fibrin, a set of coagulation factors, each of which are enzymes, need to be activated.
These enzymes are activated via a process called proteolysis- which is where a portion
of the protein is clipped off.
In total, there are twelve coagulation factors numbered factors I-XIII, there’s no factor
VI.
Most of these factors are produced by liver cells, and it turns out that producing coagulation
factors II, VII, IX, and X requires an enzyme that uses vitamin K.
Vitamin K is found in abundance in green leafy foods—things like spinach, kale, and chard
which all have high concentrations of vitamin K.
It’s a fat-soluble vitamin, along with vitamins A, D, and E, meaning that it can be stored
in fat cells instead of being excreted by the kidneys.
Vitamin K is also synthesized by bacteria in our gastrointestinal tract as a byproduct
of their metabolism, which further contributes to overall intake.
Now, when vitamin K is mobilized from fat cells or the digestive tract to the liver,
it’s in its dietary form and it’s called vitamin k quinone.
An enzyme, called quinone reductase, takes electrons from NADPH, and donates them to
vitamin K quinone, converting it into the reduced form which is called vitamin K hydroquinone.
Then, vitamin K hydroquinone acts as a cofactor by donating its electrons to an enzyme called
gamma glutamyl carboxylase, which converts the non-functional forms of coagulation factors
II, VII, IX, and X into their functional forms.
Gamma glutamyl carboxylase adds a carboxyl group, a chemical group made up of one carbon,
two hydrogens, and one oxygen, onto the end of glutamic acid residues on the proteins.
After the carboxylation step, vitamin K is in an oxidized form, where it can accept electrons,
and it’s called vitamin K epoxide.
Vitamin K epoxide gets converted back into vitamin K quinone by another enzyme called
epoxide reductase, which donates electrons to vitamin K epoxide using a thiol group.
In this fashion, a single molecule of vitamin K can be reused many times.
As it turns out, the drug warfarin, which was first used as a rat poison, blocks the
function of this enzyme which blocks vitamin K from getting recycled and as a result factors
II, VII, IX, and X don’t get activated.
Now let's take a closer look at the coagulation cascade to see where these coagulation factors
play their respective roles.
The coagulation cascade begins via two pathways --the extrinsic and intrinsic pathways.
The intrinsic pathway starts when circulating factor XII comes into contact with the surface
of activated platelets or collagen.
Activated factor XII, then activates factor XI, which activates factor IX which activates
factor X. Factor X starts the common pathway where it activates factor II, which activates
factor I that builds the fibrin mesh.
When factor II gets activated it also activates 4 other factors: V, VIII, XI, and XIII.
Factor V gets activated and acts as a cofactor for X, factor VIII acts as a cofactor for
factor IX, and factor XIII helps factor I, or fibrin, form crosslinks.
In the extrinsic pathway, exposed tissue factor activates factor VII, which activates factor
X and starts the common pathway.
So without vitamin K, the loss of factor VII means that the extrinsic pathway won’t function;
and without factor IX, the extrinsic pathway won’t function; and without factor X and
II, the common pathway won’t function.
Since these factors are utilized in all three pathways, it’s easy to see how clot formation
does not function properly unless our body properly utilizes vitamin K.
Alright, as a quick recap vitamin K plays an essential role in clot formation because
it’s used in the synthesis of clotting factors II, VII, IX, and X.
In order to be useful, vitamin K undergoes a series of oxidation and reduction reactions
called the vitamin K cycle.
An important target of this system is the drug warfarin, which inhibits epoxide reductase
to prevent maturation of these factors.