Metabolism and cell biology of vitamin K.
Naturally occurring vitamin K compounds comprise a plant form, phylloquinone (vitamin K(1)) and a series of bacterial menaquinones (MKs) (vitamin K(2)). 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 K(2) 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.
Centre for Haemostasis and Thrombosis, St Thomas' Hospital, Westminster Bridge Road, London, UK. martin.shearer@gstt.nhs.uk
Martin J
MJ
Shearer
Paul
P
Newman
D000818:Animals; D000925:Anticoagulants / Q000737:chemistry / Q000493:pharmacokinetics; D001798:Blood Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D010011:Osteocytes / Q000378:metabolism*; D014812:Vitamin K / Q000737:chemistry / Q000378:metabolism*; D010837:Vitamin K 1 / Q000737:chemistry / Q000493:pharmacokinetics; D024482:Vitamin K 2 / Q000737:chemistry / Q000493:pharmacokinetics; D014813:Vitamin K Deficiency / Q000378:metabolism*
D000925:Anticoagulants; D001798:Blood Proteins; D024482:Vitamin K 2; D014812:Vitamin K; D010837:Vitamin K 1