title: Comparative uptake, metabolism, and utilization of menaquinone-4 and phylloquinone in human cultured cell lines.
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 18O-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 (18O-, 16O-quinone, and epoxide forms) was carried out with LC-APCI-MS/MS as previously reported. The 18O of vitamin K was replaced with atmospheric 16O2 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 18O-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 18O-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.
authors.affiliation: Department of Hygienic Sciences, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Kobe 658-8558, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Suhara
authors.forename: Aya
authors.initials: A
authors.lastname: Murakami
authors.forename: Kimie
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Yukari
authors.initials: Y
authors.lastname: Mizuguchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Okano
mesh_terms: D002138:Calibration; D002460:Cell Line; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D012015:Reference Standards; D014812:Vitamin K / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D010837:Vitamin K 1 / Q000737:chemistry / Q000378:metabolism*; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
chemical_list: D007202:Indicators and Reagents; D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; D010837:Vitamin K 1