Vitamin K1 2,3-epoxide
[CAS# 25486-55-9]

Identification

• Classification: Chemical reagent >> Organic reagent >> Epoxide
• Name: Vitamin K1 2,3-epoxide
• Synonyms: (2,3-Epoxyphytyl)menaquinone
• Molecular Formula: C₃₁H₄₆O₃
• Molecular Weight: 466.69
• CAS Registry Number: 25486-55-9
• EC Number: 247-022-9
• SMILES: CC(C)CCCC(C)CCCC(C)CCC/C(=C/CC12C(=O)C3=CC=CC=C3C(=O)C1(O2)C)/C

Properties

• Density: 1.0±0.1 g/cm³ Calc.^*
• Boiling point: 561.1±50.0 °C 760 mmHg (Calc.)^*
• Flash point: 233.8±30.2 °C (Calc.)^*
• Index of refraction: 1.523 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319
• Safety Statements: P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Discovery and Applications

Vitamin K₁ 2,3-epoxide is a biologically important compound formed as a result of the vitamin K cycle, a critical biochemical pathway involved in blood coagulation. It is a metabolic derivative of phylloquinone (vitamin K₁) generated during the carboxylation of specific glutamate residues on vitamin K–dependent proteins.

The discovery of vitamin K and its metabolic cycle dates back to the 1930s and 1940s, when researchers identified its essential role in blood clotting. During this process, vitamin K₁ acts as a cofactor for the enzyme γ-glutamyl carboxylase, which catalyzes the post-translational modification of glutamate residues to γ-carboxyglutamate (Gla) on coagulation factors such as prothrombin (factor II), factor VII, factor IX, and factor X. This reaction is essential for enabling these proteins to bind calcium and function effectively in the coagulation cascade.

In the carboxylation reaction, vitamin K₁ undergoes oxidation and is converted into vitamin K₁ 2,3-epoxide. To sustain the cycle, this epoxide form must be reduced back to the active hydroquinone form of vitamin K₁ through two sequential reduction steps. These reactions are catalyzed by vitamin K epoxide reductase (VKOR) enzymes. The VKOR complex reduces the epoxide to vitamin K quinone and then to the hydroquinone form, which can again serve as a cofactor for carboxylase enzymes.

The vitamin K₁ epoxide form itself does not possess biological activity in coagulation but is crucial as an intermediate in the regeneration of active vitamin K₁. The proper functioning of this cycle ensures a continuous supply of vitamin K₁ in its active form, thereby maintaining the activation of coagulation proteins.

Clinically, the significance of vitamin K₁ 2,3-epoxide is closely related to the mechanism of action of anticoagulant drugs such as warfarin. Warfarin inhibits the VKOR enzyme, thereby blocking the reduction of vitamin K₁ 2,3-epoxide back to the active form. This disruption leads to a decrease in the carboxylation of clotting factors, resulting in an anticoagulant effect. Measurement of vitamin K₁ 2,3-epoxide levels in plasma has been explored in some clinical studies to assess warfarin activity or vitamin K status.

The accumulation of vitamin K₁ 2,3-epoxide may occur during anticoagulant therapy or in cases of vitamin K deficiency, which can affect the efficiency of blood coagulation. However, under normal physiological conditions, the vitamin K cycle operates efficiently, and the epoxide form is rapidly converted back to active vitamin K₁.

In summary, vitamin K₁ 2,3-epoxide is a key intermediate in the vitamin K cycle formed during the γ-carboxylation of clotting factors. While it lacks direct biological activity, its presence and reconversion are essential for maintaining the active pool of vitamin K₁ and ensuring the proper functioning of the coagulation system.

References

2014. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. Journal of Lipid Research, 55(3).
DOI: 10.1194/jlr.r045559

2011. Functional study of the vitamin K cycle in mammalian cells. Blood, 117(10).
DOI: 10.1182/blood-2010-08-304303

2014. Rapid, high performance method for the determination of vitamin K(1), menaquinone-4 and vitamin K(1) 2,3-epoxide in human serum and plasma using liquid chromatography-hybrid quadrupole linear ion trap mass spectrometry. Journal of chromatography. A, 1338.
DOI: 10.1016/j.chroma.2014.02.065