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Vitamin K and the synthesis and function of gamma-carboxyglutamic acid

Bruce Furie, MD
Beth A Bouchard, PhD
Barbara C Furie, PhD
Section Editor
Lawrence LK Leung, MD
Deputy Editor
Jennifer S Tirnauer, MD


Vitamin K is a cofactor for the enzymatic conversion of glutamic acid (Glu) residues to gamma-carboxyglutamic acid (Gla) in vitamin K-dependent proteins, via the endoplasmic reticulum resident vitamin K-dependent gamma-glutamyl carboxylase. This carboxylase activity is found in essentially all mammalian tissues, and its reaction product, Gla, has been observed in both vertebrates and invertebrates; both play an important biological role in protein function [1].

The functions of Gla and the vitamin K-dependent biosynthesis of Gla will be discussed here. An overview of the blood coagulation cascade is presented separately. (See "Overview of hemostasis".)


Vitamin K and its association with blood coagulation were initially described in the 1920s and 1930s, following investigation of a hemorrhagic disease of cattle caused by ingestion of spoiled sweet clover [2]. Since then, a number of observations, which will be discussed in detail below, have improved our understanding of the biological role of vitamin K [3]:

Discovery of vitamin K antagonists and their introduction as pharmacologic agents for anticoagulation (ie, the coumarins) [4].

Discovery of Gla in blood clotting proteins [5,6].

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Literature review current through: Nov 2017. | This topic last updated: Feb 22, 2017.
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