Advertisement
Advertisement

Contact Person

Dr. Elinor Switzer

Managing Editor

Phone: +49 (0)711 - 2 29 87 63
Fax: +49 (0)711 - 2 29 87 65
send an Email


Archive

Metabolism and cell biology of vitamin K

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Topic:

New vitamin K-dependent proteins

DOI: http://dx.doi.org/10.1160/TH08-03-0147
Issue: 2008: 100/4 (Oct) pp. 517-726
Pages: 530-547

Metabolism and cell biology of vitamin K

Martin J. Shearer1, Paul Newman2

1Centre for Haemostasis and Thrombosis, Guy’s & St Thomas’ NHS Foundation Trust, London, UK; 2Epithelial Cell Biology Laboratory, Cancer Research UK, Cambridge Research Institute, Cambridge

Keywords

oral anticoagulants, metabolism, vitamin K, phylloquinone, menaquinones, cell biology, Gla-proteins

Summary

Naturally occurring vitamin K compounds comprise a plant form, phylloquinone (vitamin K1) and a series of bacterial menaquinones (MKs) (vitamin K2). Structural differences in the isoprenoid side chain govern many facets of metabolism of K vitamins including the way they are transported, taken up by target tissues, and subsequently excreted. In the post-prandial state, phylloquinone is transported mainly by triglyceride-rich lipoproteins (TRL) and long-chain MKs mainly by low-density lipoproteins (LDL).TRL-borne phylloquinone uptake by osteoblasts is an apoE-mediated process with the LRP1 receptor playing a predominant role. One K2 form, MK-4, has a highly specific tissue distribution suggestive of local synthesis from phylloquinone in which menadione is an intermediate. Both phylloquinone and MKs activate the steroid and xenobiotic receptor (SXR) that initiates their catabolism, but MK-4 specifically upregulates two genes suggesting a novel MK-4 signalling pathway. Many studies have shown specific clinical benefits of MK-4 at pharmacological doses for osteoporosis and cancer although the mechanism(s) are poorly understood. Other putative non-cofactor functions of vitamin K include the suppression of inflammation, prevention of brain oxidative damage and a role in sphingolipid synthesis. Anticoagulant drugs block vitamin K recycling and thereby the availability of reduced vitamin K. Under extreme blockade, vitamin K can bypass the inhibition of Gla synthesis in the liver but not in the bone and the vessel wall. In humans, MK-7 has a greater efficacy than phylloquinone in carboxylating both liver and bone Gla proteins. A daily supplement of phylloquinone has shown potential for improving anticoagulation control.

You may also be interested in...

1.
Ellen C. M. Cranenburg, Leon J. Schurgers, Cees Vermeer

Thromb Haemost 2007 98 1: 120-125

http://dx.doi.org/10.1160/TH07-04-0266

2.

Leon J. Schurgers, Ellen C. M. Cranenburg, Cees Vermeer

Thromb Haemost 2008 100 4: 593-603

http://dx.doi.org/10.1160/TH08-02-0087

3.
Anetta Undas1, Beata Brzezinska-Kolarz1, Tom Orfeo2, Kathleen Brummel-Ziedins2, Jacek Musial1, Andrew Szczeklik1, Kenneth G. Mann2

Thromb Haemost 2007 98 5: 1024-1030

http://dx.doi.org/10.1160/TH07-04-0302