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(Circulation. 2006;113:1550-1552.)
© 2006 American Heart Association, Inc.

Editorial

Vitamin K Epoxide Reductase Complex and Vascular Calcification

Is This the Important Link Between Vitamin K and the Arterial Vessel Wall?

Henri M.H. Spronk, PhD

From the Department of Internal Medicine, Maastricht University, Maastricht, The Netherlands.

Correspondence to Henri M.H. Spronk, PhD, Department of Internal Medicine, Maastricht University, PO Box 616, UNS50 Box 8, 6200 MD Maastricht, The Netherlands. E-mail henri.spronk@bioch.unimaas.nl

Key Words: Editorials • atherosclerosis • coagulation • risk factors • thrombosis

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Vitamin K is a cofactor in the -glutamyl carboxylation pathway, a posttranslational conversion of specific glutamate residues into -carboxyglutamic acid (Gla) residues, catalyzed by the endoplasmic reticulum enzyme -glutamyl carboxylase. The substrates of carboxylase are the so-called vitamin K–dependent proteins, which are involved in diverse physiological processes such as blood coagulation, bone and soft tissue mineralization, and cellular proliferation. The coagulation factors II (prothrombin), VII, IX, and X have procoagulant activity, whereas proteins C and S inhibit blood coagulation (see reviews by Dahlback¹ and Stafford²). Protein Z is involved in the fixation of thrombin by binding to a phospholipid surface. Matrix Gla protein (MGP) and osteocalcin (or bone Gla protein) are regulators of tissue mineralization, whereas Gas6 is involved in the regulation of cell growth. The mRNA sequences of 4 new putative vitamin K–dependent proteins were recently reported, but their functions remain elusive: 2 proline-rich Gla proteins, PRGP1 and PRGP2, and 2 transmembrane Gla proteins, TMG3 and TMG4. For each of these proteins, the presence of Gla residues is a prerequisite for Ca²⁺ binding and/or Ca²⁺-dependent interaction with negatively charged surfaces. Four key components are involved in the proper biosynthesis of the vitamin K–dependent proteins: the enzymes -glutamyl carboxylase and vitamin K epoxide reductase complex (VKORC1), vitamin K, and a precursor protein. Not the form in which it occurs in food (vitamin K quinone) but the reduced form, vitamin K hydroquinone (KH₂), is the active cofactor used by the enzyme -glutamyl carboxylase (Figure). KH₂ is . . . [Full Text of this Article]

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