New Developments in Research on Vitamin K Biosynthesis
スポンサーリンク
概要
- 論文の詳細を見る
Phylloquinone (PK) is a major form of dietary vitamin K; however, the most prevalent form of vitamin K in humans and animals is menaquinone-4 (MK-4). Despite its high concentrations, the origin of MK-4 is yet to be defined. It is postulated that PK is converted into MK-4 and accumulates in extrahepatic tissues. To clarify this, PK with a deuterium-labelled 2-methyl-1,4-naphthoquinone ring was administered orally to mice and their cerebra were collected for deuterium (D) NMR and liquid chromatography (LC)-MS/MS analyses. We identified labelled MK-4 formed by conversion of the given PK, and this conversion occurred following oral or enteral administration but not parenteral or intracerebroventrical administration. Through the oral route, PK with the deuterium-labelled side chain in addition to the labelled 2-methyl-1,4-naphthoquinone was clearly converted into labelled MK-4 with a non-deuterium-labelled side chain, implying that PK was converted into MK-4 via the removal of an integral side chain. Our results suggest that cerebral MK-4 originates from PK intake, comprising the release of menadione (K3) from PK in the intestine followed by prenylation of K3 into MK-4 in the intestine or other tissues. We recently demonstrated that deuterium-labelled PK (PK-d7) and deuterium-labelled K3 (K3-d8) are converted to deuterium-labelled MK-4 (MK-4-d7) in human osteoblast-like MG-63 cells. Moreover, we identified that the side chain substrate involved in the conversion of PK or K3 to MK-4 is geranylgeranyl diphosphate deriving from the mevalonate pathway. Therefore, MK-4 biosynthesis likely plays an important role in biological functions of the brain and bones.
- 社団法人 日本薬学会の論文
著者
関連論文
- Synthesis of γ-Hydroxybutenolides Applying Crossed Aldol Condensation in the Presence of a Bulky Lewis Acid and Their Anti-tumor Activity
- Antitumoral Activity of 13-Demethyl or 13-Substituted Analogues of All-trans Retinoic Acid and 9-cis Retinoic Acid in the Human Myeloid Leukemia Cell Line HL-60(Biochemistry)
- Biological Activities of 2α-Substituted Analogues of 1α, 25-Dihydroxyvitamin D_3 in Transcriptional Regulation and Human Promyelocytic Leukemia (HL-60) Cell Proliferation and Differentiation(Medicinal Chemistry)
- Synthesis and Biological Evaluation of 9Z-Retinoic Acid Analogs Having 2-Substituted Benzo[b]furan
- In Vitro Biological Activities of a Series of 2β-Substituted Analogues of 1α, 25-Dihydroxyvitamin D_3
- Rapid Control of Transmembrane Calcium Influx by 1α, 25-Dihydroxyvitamin D_3 and Its Analogues in Rat Osteoblast-Like Cells
- Singly Dehydroxylated A-Ring Analogues of 19-Nor-1α, 25-dihydroxyvitamin D_3 and 19-Nor-22-oxa-1α, 25-dihydroxyvitamin D_3 : Novel Vitamin D_3 Analogues with Potent Transcriptional Activity but Extremely Low Affinity for Vitamin D Receptor
- New Developments in Research on Vitamin K Biosynthesis
- Absorption of Calcium, Magnesium, Phosphorus, Iron and Zinc in Growing Male Rats Fed Diets Containing either Phytate-free Soybean Protein or Soybean Protein Isolate or Casein
- Intestinal absorption of calcium from calcium ascorbate in rats
- Biological Activity Profiles of 1α, 25-Dihydroxyvitamin D_2,D_3,D_4,D_7,and 24-Epi-1α, 25-dihydroxyvitamin D_2