undercarboxylated

Undercarboxylated is an adjective used in biochemistry and medicine to describe proteins that have not undergone full gamma-carboxylation of certain glutamate residues to gamma-carboxyglutamate (Gla). Gamma-carboxylation is a vitamin K–dependent post-translational modification carried out by gamma-glutamyl carboxylase, using reduced vitamin K as a cofactor. This modification enables calcium binding and proper function for several proteins.

Undercarboxylation occurs when vitamin K status is insufficient or when the carboxylation machinery is impaired. Contributing factors include poor dietary intake, fat malabsorption, liver disease, use of vitamin K antagonists such as warfarin, or genetic variations affecting the enzyme. As a result, these proteins have fewer Gla residues and reduced calcium-binding capacity, compromising their activity.

Common examples include undercarboxylated prothrombin (PIVKA-II), an early marker of vitamin K deficiency and a reference in monitoring anticoagulation; undercarboxylated osteocalcin (ucOC), a bone-derived protein whose carboxylation status is studied in relation to bone metabolism and vitamin K status; and undercarboxylated matrix Gla protein (ucMGP), linked to the regulation of vascular calcification. The proportion of undercarboxylated forms in blood or tissues serves as a biomarker of vitamin K status and the functional adequacy of vitamin K–dependent proteins.

Measurement methods include immunoassays for PIVKA and specific assays for ucOC and ucMGP. Clinically, maintaining adequate vitamin K intake supports proper carboxylation and the normal function of these vitamin K–dependent proteins.