The metabolic role of vitamin K

Abstract

Vitamin K is a required cofactor for a microsomal enzyme system that carboxylates glutamyl residues of precursor proteins to gamma-carboxyglutamyl residues in completed proteins. These residues have recently been shown to be present in a number of proteins other than the long-recognized vitamin K-dependent clotting factors, and it is apparent that this reaction is much more widespread than once thought. This enzyme has been extensively studied in rat liver and has been shown to require the reduced form of vitamin K, O2, and CO2. This enzyme activity is induced in vitamin K-deficient animals, and the activity has been localized at the lumen surface of the rough microsome fraction. Liver microsomes also contain enzymes that oxidize the vitamin to its 2,3-epoxide and reduce the epoxide back to the reduced vitamin. The carboxylase activity and epoxidase activity appear to share a common oxygenated intermediate, and the available data suggest that this may be a hydroperoxide of the vitamin. Current evidence would indicate that the role of vitamin K is to labilize the gamma-hydrogen of the substrate for CO2 attack rather than to activate or transfer the CO2.