Vitamin K (Phytonadione and Menaquinones)

Mechanism

🌿 Vitamin K1 (Phylloquinone)

• Origin: Naturally present in green leafy vegetables.
• Function: It constitutes the main human dietary source.
• It has a high affinity for the hepatic synthesis of plasma coagulation factors.

🦠 Vitamin K2 (Menaquinones)

• Origin: Synthesized by bacteria from the intestinal microbiota of the genera Bacteroides and Escherichia.
• Function: It has a long tissue half-life.
• It is widely distributed to peripheral tissues such as bone and intestinal tissue.

Mechanism of action: The vitamin K cycle

Vitamin K functions as an obligate cofactor for the microsomal enzyme γ-glutamyl carboxylase (GGCX). This enzyme adds a carboxyl group to specific glutamic acid (Glu) residues on target proteins, converting them to active γ-carboxyglutamic acid (Gla) residues. This carboxylation modification introduces two negative charges on the lateral amino acid residues, allowing the electrostatic binding of calcium cations (Ca²⁺), which facilitates their subsequent interaction with the anionic phospholipids of the cellular platelet membrane.

The reaction proceeds through a continuous cyclic redox cycle:

To maintain the catalytic activity of GGCX, the resulting inactive vitamin K epoxide must be recycled back to the active reduced form (hydroquinone). This step is carried out in two stages:

1. The enzyme Vitamin K Epoxide Reductase (VKORC1) reduces epoxide to vitamin K quinone.
2. Subsequently, another reductase reduces the quinone to active vitamin K hydroquinone.

Pharmacokinetics

Pharmacokinetics

• Absorption: Phylloquinone is absorbed in the jejunum and ileum through an active transport process dependent on lipid transporters. Bacterial menaquinones are passively absorbed in the distal colon in a variable manner, always requiring a lipid gradient.
• Metabolism: It is rapidly metabolized in the liver by shortening the isoprenoid side chain, becoming polar metabolites eliminated primarily by biliary excretion conjugated with glucuronic acid. Its liver reserves are very limited compared to other fat-soluble vitamins.

Indicators and dose

Clinical Indications and Neonatal Prophylaxis

• Hemorrhagic Disease of the Newborn (Mandatory Prophylaxis): Newborns have extremely low hepatic stores of vitamin K, an immature intestinal microbiota, and breast milk that is poor in phylloquinone. Therefore, a dose of 1 mg intramuscular phytonadione is universally administered in the anterolateral thigh in the first 6 hours of postpartum life to prevent severe hemorrhages of cranial or digestive origin.
• Reversal of Anticoagulation by Coumarins: Indicated to correct excessive INR or bleeding associated with warfarin. It is dosed according to the clinical risk of bleeding.

Security

Critical Interaction with Coumarin Anticoagulants

Oral anticoagulants such as warfarin and acenocoumarol are potent irreversible competitive inhibitors of the VKORC1 enzyme. By blocking this enzyme, they prevent the regeneration of the reduced form of vitamin K (hydroquinone), which interrupts the carboxylation of vitamin K-dependent coagulation factors (Factors II, VII, IX and X, as well as anticoagulant proteins C and S), significantly reducing their functional hemostatic capacity.