TY - JOUR
T1 - Elucidation of the mechanism producing menaquinone-4 in osteoblastic cells
AU - Suhara, Yoshitomo
AU - Wada, Akimori
AU - Okano, Toshio
N1 - Funding Information:
We are grateful to Dr. Makiko Sugiura, Dr. Atsuko Takeuchi, and Dr. Chisato Tode for the spectroscopic measurements. We also thank Eisai Co., Ltd for generously providing the intermediate of the vitamin K analogues. This study was supported in part by a Grant-in-Aid for Scientific Research ⟨KAKENHI⟩ (C) (Grant No. 18590112) from the Japan Society for the Promotion of Science and a grant from the Promotion and Mutual Aid Corporation for Private Schools of Japan.
PY - 2009/2/15
Y1 - 2009/2/15
N2 - Vitamin K is an essential nutrient and a cofactor for the carboxylation of specific glutamyl residues of proteins to γ-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.
AB - Vitamin K is an essential nutrient and a cofactor for the carboxylation of specific glutamyl residues of proteins to γ-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.
KW - Geranylgeranylpyrophosphate
KW - Mechanism
KW - Menaquinone-4
KW - Mevalonate pathway
KW - Osteoblastic cells
KW - Vitamin K
UR - http://www.scopus.com/inward/record.url?scp=59649101808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59649101808&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2009.01.021
DO - 10.1016/j.bmcl.2009.01.021
M3 - Article
C2 - 19167887
AN - SCOPUS:59649101808
SN - 0960-894X
VL - 19
SP - 1054
EP - 1057
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 4
ER -