Other Probably Non Gla Functions of Vitamin K

Vitamin K is thought to be involved in sphingolipid metabolism in certain bacteria by modulating serine palmitoyl transferase, and warfarin treatment decreased brain levels of sulfatides and galactocere-broside sulfotransferase activity in animals, which was reversible by vitamin K (either K1 or MK-4). Therefore, it is now thought that vitamin K may be involved in sphingolipid metabolism, and this in turn has implications for its action as a second messenger as well as being a structural component. There are several functions of MK-4 that are shared by the isolated geranyl-geraniol side chain, which involve the induction of apoptosis of osteoclasts and of certain cancer cells in culture. Depriving certain tumours of vitamin K, both in vitro and in vivo, seemed to inhibit their growth and metastasis. Patients receiving warfarin for cardiovascular disease seem to have a reduced incidence of tumors, and warfarin may also suppress delayed-type hypersensitivity reactions.

Recent studies have suggested that MK-4, in particular, has a transcriptional regulatory function, for example, in osteosarcoma cell cultures, in which it binds to and activates the SXR steroid and xenobiotic receptor. This in turn increases mRNA levels for osteo-blast markers: bone alkaline phosphatase, osteoproto-gerin, osteopontin, and MGP. MK-4 and its isolated geranyl-geraniol side chain was also able to suppress the synthesis of prostaglandin E2, which is a potent bone resorption catalyst. These observations have led to speculation (i) that some of the menaquinones may possess some functions that are not shared by phyllo-quinone, and (ii) that there may be implications for cell proliferation and for cancer risk from variations in the supply of vitamin K and in its speciation.

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