Comparative uptake, metabolism, and utilization of menaquinone-4 and phylloquinone in human cultured cell lines. Export

@article{citeulike:788560, abstract = {It is generally accepted that the availability of vitamin K in vivo depends on its homologues, the biological activities of which would differ among organs. To test this hypothesis, we examined the uptake, metabolism, and utilization of menaquinone-4 (MK-4) and phylloquinone (PK) using (18)O-labeled compounds in two cultured human cell lines (HepG2 and MG-63). Lipid extracts were prepared from the cells and media after 1, 3, and 6h of incubation. The detection of the vitamin K analogues ((18)O-, (16)O-quinone, and epoxide forms) was carried out with LC-APCI-MS/MS as previously reported. The (18)O of vitamin K was replaced with atmospheric (16)O(2) during the formation of vitamin K epoxide with a carboxylative catalytic reaction. As a result, a significant difference was observed between MK-4 and PK in the amounts taken up into the cells. The (18)O-labeled MK-4 was rapidly and remarkably well absorbed into the cells and metabolized to the epoxide form via a hydroquinone form as compared to the (18)O-labeled PK. The difference in uptake of MK-4 and PK was not affected by treatment with warfarin although the metabolism of both compounds was markedly inhibited. This methodology should be utilized to clarify some of the actions of vitamin K in target cells and facilitate the development of new vitamin K drugs.}, address = {Department of Hygienic Sciences, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.}, author = {Suhara, Yoshitomo and Murakami, Aya and Nakagawa, Kimie and Mizuguchi, Yukari and Okano, Toshio}, citeulike-article-id = {788560}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.bmc.2006.06.004}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16798001}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16798001}, day = {22}, doi = {10.1016/j.bmc.2006.06.004}, issn = {0968-0896}, journal = {Bioorg Med Chem}, keywords = {hplc, vitamink}, month = {June}, posted-at = {2006-08-07 10:32:15}, priority = {3}, title = {Comparative uptake, metabolism, and utilization of menaquinone-4 and phylloquinone in human cultured cell lines.}, url = {http://dx.doi.org/10.1016/j.bmc.2006.06.004}, year = {2006} }

TY - JOUR ID - citeulike:788560 L3 - citeulike-article-id:788560 N2 - It is generally accepted that the availability of vitamin K in vivo depends on its homologues, the biological activities of which would differ among organs. To test this hypothesis, we examined the uptake, metabolism, and utilization of menaquinone-4 (MK-4) and phylloquinone (PK) using (18)O-labeled compounds in two cultured human cell lines (HepG2 and MG-63). Lipid extracts were prepared from the cells and media after 1, 3, and 6h of incubation. The detection of the vitamin K analogues ((18)O-, (16)O-quinone, and epoxide forms) was carried out with LC-APCI-MS/MS as previously reported. The (18)O of vitamin K was replaced with atmospheric (16)O(2) during the formation of vitamin K epoxide with a carboxylative catalytic reaction. As a result, a significant difference was observed between MK-4 and PK in the amounts taken up into the cells. The (18)O-labeled MK-4 was rapidly and remarkably well absorbed into the cells and metabolized to the epoxide form via a hydroquinone form as compared to the (18)O-labeled PK. The difference in uptake of MK-4 and PK was not affected by treatment with warfarin although the metabolism of both compounds was markedly inhibited. This methodology should be utilized to clarify some of the actions of vitamin K in target cells and facilitate the development of new vitamin K drugs. JF - Bioorg Med Chem SN - 0968-0896 AD - Department of Hygienic Sciences, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan. TI - Comparative uptake, metabolism, and utilization of menaquinone-4 and phylloquinone in human cultured cell lines. KW - hplc KW - vitamink AU - Suhara, Yoshitomo AU - Murakami, Aya AU - Nakagawa, Kimie AU - Mizuguchi, Yukari AU - Okano, Toshio PY - 2006/06/22/ UR - http://dx.doi.org/10.1016/j.bmc.2006.06.004 ER -