Metabolism and cell biology of vitamin K

Martin J. Shearer; Paul Newman

doi:10.1160/TH08-03-0147

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(04): 530-547
DOI: 10.1160/TH08-03-0147

Theme Issue Article

Schattauer GmbH

Metabolism and cell biology of vitamin K

Authors

Martin J. Shearer

¹Centre for Haemostasis and Thrombosis, Guy’s & St Thomas’ NHS Foundation Tr ust, London, UK
Paul Newman

²Epithelial Cell Biology Laboratory, Cancer Research UK, Cambridge Research Institute, Cambridge

Abstract

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.

Keywords

Vitamin K - phylloquinone - menaquinones - metabolism - cell biology - Gla-proteins - oral anticoagulants

Full Text

References

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