Extra-Hepatic Functions of Vitamin K

Vitamin K was discovered in 1929 as a substance essential for blood coagulation, and had been clinically utilized before the precise mechanism of action became aware in 1970s. The function as a co-factor of γ-glutamyl carboxylase (GGCX) was the mechanism firstly discovered with the identification of several substrate proteins including blood coagulation factors generated in the liver. Recently, we and others have revealed that vitamin K has other modes of function, such as a ligand of nuclear receptor SXR (steroid and xenobiotic receptor) and its murine ortholog PXR (pregnane X receptor), covalent modifier of a protein, and antioxidant protecting from ferroptosis. Besides its importance in hepatic function concerning blood coagulation, involvement of vitamin K has been shown in several extra-hepatic organs or tissues. Clinical trials, epidemiological studies, and basic studies using animal models suggest wide range of vitamin K functions throughout the body. Although persuasive evidences of interventional study are still not sufficient, vitamin K has a potential for prevention and treatment for related conditions or diseases.