Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 19, Issue 4, Pages 1054-1057Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2009.01.021
Keywords
Vitamin K; Menaquinone-4; Mechanism; Osteoblastic cells; Geranylgeranylpyrophosphate; Mevalonate pathway
Categories
Funding
- Japan Society [18590112]
- Promotion and Mutual Aid Corporation for Private Schools of Japan
- Grants-in-Aid for Scientific Research [18590112] Funding Source: KAKEN
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Vitamin K is an essential nutrient and a cofactor for the carboxylation of specific glutamyl residues of proteins to gamma-glutamyl residues, which activates osteocalcin related to bone formation. Among vitamin K homologues, menaquinone-4 (MK-4) is the most active biologically, up-regulating the gene expression of bone markers, and thus has been clinically used in the treatment of osteoporosis in Japan. Recently, we confirmed that MK-4 was converted from dietary phylloquinone (PK), and then accumulated in various tissues at high concentrations. This system should play an important role in biological functions including bone formation, however, the pathway by which MK- 4 is converted remains unclear. In this study, we studied the mechanism of MK-4's conversion with chemical techniques using deuterated analogues. (C) 2009 Elsevier Ltd. All rights reserved.
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