Hostname: page-component-78c5997874-t5tsf Total loading time: 0 Render date: 2024-11-09T01:32:38.814Z Has data issue: false hasContentIssue false
  • English
  • Français

Menadione is a metabolite of oral vitamin K

Published online by Cambridge University Press:  08 March 2007

Henk H. W. Thijssen ,
Lily M. T. Vervoort ,
Leon J. Schurgers  and
Martin J. Shearer
Henk H. W. Thijssen*
Affiliation:
Department of Pharmacology, Cardiovascular Research Institute Maastricht, University of MaastrichtPO Box 616, 6200 MD Maastricht, The Netherlands
Lily M. T. Vervoort
Affiliation:
Department of Pharmacology, Cardiovascular Research Institute Maastricht, University of MaastrichtPO Box 616, 6200 MD Maastricht, The Netherlands
Leon J. Schurgers
Affiliation:
Department of Biochemistry, University of Maastricht, The Netherlands
Martin J. Shearer
Affiliation:
The Centre for Haemostasis and Thrombosis, St. Thomas's Hospital, London, UK
*
*Corresponding author: Dr Henk H. W. Thijssen, fax +31 43 3884149, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Phylloquinone is converted into menaquinone-4 and accumulates in extrahepatic tissues. Neither the route nor the function of the conversion is known. One possible metabolic route might be the release of menadione from phylloquinone by catabolic activity. In the present study we explored the presence of menadione in urine and the effect of vitamin K intake on its excretion. Menadione in urine was analysed by HPLC assay with fluorescence detection. Urine from healthy male volunteers was collected before and after administration of a single dose of K vitamins. Basal menadione excretion in non-supplemented subjects (n 6) was 5·4 (sd 3·2) μg/d. Urinary menadione excretion increased greatly after oral intake of the K vitamins, phylloquinone and menaquinone-4 and -7. This effect was apparent within 1–2h and peaked at about 3h after intake. Amounts of menadione excreted in 24h after vitamin K intake ranged, on a molar basis, from 1 to 5% of the administered dose, indicating that about 5–25% of the ingested K vitamins had been catabolized to menadione. Menadione excretion was not enhanced by phylloquinone administered subcutaneously or by 2′,3′-dihydrophylloquinone administered orally. In archived samples from a depletion/repletion study (Booth et al. (2001)Am J Clin Nutr74, 783–790), urinary menadione excretion mirrored dietary phylloquinone intake. The present study shows that menadione is a catabolic product of K vitamins formed after oral intake. The rapid appearance in urine after oral but not subcutaneous administration suggests that catabolism occurs during intestinal absorption. The observations make it likely that part of the menaquinone-4 in tissues results from uptake and prenylation of circulating menadione

Keywords

MenadionePhylloquinoneMetabolismMenaquinone-4Vitamin K
Type
Research Article
Information
British Journal of Nutrition , Volume 95 , Issue 2 , February 2006 , pp. 260 - 266
Copyright
Copyright © The Nutrition Society 2006

References

Berkner, KL & Runge, KWThe physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis. J Thromb Haemost 2005 2 2118–2132CrossRefGoogle Scholar
Billeter, MBollinger, W&Martius, CUntersuchungen über die Umwandlung von verfütterten K-vitaminen durch austauch der Seitenkette und die rolle der Darmbakterien hierbei. Biochem Z 1964 340 290–303Google Scholar
Billeter, M&Martius, CÜ ber die Umwandlung von Phyllochinon (Vitamin K1) in Vitamin K2(20) in Tierkörper. Biochem Z 1960 333 430–439Google Scholar
Booth, SLLichtenstein, AHAH,, M, McKeown, NMWood, RJSaltzman, E & Gundberg, CMEffects of a hydrogenated form of vitamin K on bone formation and resorption Am J Clin Nutr 2001 74 783–790CrossRefGoogle ScholarPubMed
Carrie, IPortoukalian, JVicaretti, RRochford, JPotvin, S &Ferland, GMenaquinone-4 concentration is correlated with sphingolipid concentrations in rat brain. J Nutr 2004 134 167–172CrossRefGoogle ScholarPubMed
Conley, JM&Stein, KThe production of menaquinones (vitamin K2) by intestinal bacteria and their role in maintaining coagulation homeostasis. Prog Food Nutr Sci 1992 16 307–343Google Scholar
Davidson, RTFoley, ALEngelke, JA &Suttie, JWConversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria. J Nutr 1998 128 220–223CrossRefGoogle Scholar
Hagstrom, JNBovill, EGSoll, RFDavidson, KW&Sadowski, JAThe pharmacokintics and lipoprotein fraction distribution of intramuscular vs. oral vitaminK1 supplementation in women of childbearing age: effects on hemostasis. Thromb Haemost 1995 74 1486–1490Google Scholar
Haroon, YBacon, DS&Sadowski, JAChemical reduction system for the detection of phylloquinone (vitamin K1) and menaquinones (vitamin K2) J Chromatogr 1987 384 383–389CrossRefGoogle ScholarPubMed
Harrington, DJSoper, REdwards, CSavidge, GFHodges, SJ&Shearer, MJDetermination of the urinary aglycone metabolites of vitamin K by HPLC with redox-mode electrochemical detection. J Lipid Res 2005 46 1053–1060CrossRefGoogle ScholarPubMed
Hu, OY-PWu, C-YChan, W-K & Wu, FY-HDetermination of anticancer drug vitamin K3 in plasma by high-performance liquid chromatography J Chromatogr 1995 666 299–305Google ScholarPubMed
Imada, IWatanabe, MMatsumoto, N&Morimoto, HMetabolism of ubiquinone-7. Biochemistry 1970 9 2870–2878CrossRefGoogle ScholarPubMed
Kohlmeier, MSalomon, ASaupe, J&Shearer, MJTransport of vitamin K to bone in humans J Nutr 1996 126Suppl. 1192S–1196SCrossRefGoogle ScholarPubMed
Lamon-Fava, SSadowski, JA, Davidson, KWO'Brien, MEMcNamara, JR&Schaefer, EJPlasma lipoproteins as carriers of phylloquinone (vitamin K1) in humans. Am J Clin Nutr 1998 67 1226–1231CrossRefGoogle ScholarPubMed
Losito, ROwen, CA&Flock, EVMetabolism of [14C]menadione. Biochemistry 1998 6 62–68CrossRefGoogle Scholar
Resh, MDMembrane targeting of lipid modified signal transduction proteins. Subcell Biochem 2004 37 217–232CrossRefGoogle ScholarPubMed
Ronden, JEDrittij-Reijnders, MJVermeer, C&Thijssen, HHWIntestinal flora is not an intermediate in the phylloquinone–menaquinone-4 conversion in the rat Biochim Biophys Acta 1998 1379 69–75CrossRefGoogle Scholar
Roskoski, RProtein prenylation: a pivotal posttranslationaln process. Biochem Biophys Res Commun 2003 303 1–7CrossRefGoogle ScholarPubMed
Sakamoto, NKimura, MHiraike, H&Itokawa, YChanges of phylloquinone and menaquinone-4 concentrations in rat live rafter oral, intravenous and intraperitoneal administration. Int J Vitam Nutr Res 1996 66 322–328Google Scholar
Sato, TOzaki, RKamo, SHara, YKonishi, SIsobe, YSaitoh, S&Harada, HThe biological activity and tissue distribution of 2,3-dihydrophylloquinone in rats. Biochim Biophys Acta 2003 1622 145–150CrossRefGoogle ScholarPubMed
Schurgers, LJ&Vermeer, CDetermination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations Haemostasis 2000 30 298–307Google ScholarPubMed
Schurgers, LJ&Vermeer, CDifferential lipoprotein transport pathways of K-vitamins in healthy subjects Biochim Biophys Acta 2002 1570 27–32CrossRefGoogle ScholarPubMed
Shearer, MJVitamin, KLancet 1995 345 229–234CrossRefGoogle Scholar
Shearer, MJRole of vitamin K and Gla proteins in the pathophysioloy of osteoporosis and vascular calcification Curr Opin Clin Nutr Metab Care 2000 3 433–438CrossRefGoogle Scholar
Shearer, MJ, McBurney, A&Barkhan, PStudies on the absorption and metabolism of phylloquinone (vitamin K1) in man Vitam Horm 1974 32 513–542CrossRefGoogle ScholarPubMed
Sundaram, KSFan, J-HEngelke, JAFoley, ALSuttie, JW&Lev, MVitamin K status influences brain sulfatide metabolism in young mice and rats J Nutr 1996 126 2746–2751Google ScholarPubMed
Taggart, WV&Matschiner, JTMetabolism of menadione-6, 7-3H in the rat. Biochemistry 1969 8 1141–1146CrossRefGoogle ScholarPubMed
Thijssen, HHW&Drittij-Reijnders, MJVitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4. Br J Nutr 1994 72 415–425CrossRefGoogle ScholarPubMed
Thijssen, HHW&Drittij-Reijnders, MJVitamin K status in human tissues: tissue-specific accumulation of phylloquinone and menaquinone-4. Br J Nutr 1996 75 121–127CrossRefGoogle ScholarPubMed
Thijssen, HHWDrittij-Reijnders, MJ&Fischer, MAJGPhylloquinonand and menaquinone-4 distribution in rats: synthesis rather than uptake determines menaquinone-4 organ concentrations. J Nutr 1996 126 537–543CrossRefGoogle ScholarPubMed
Thijssen, HHWDrittij, MJVermeer, C&Schoffelen, EMenaquinone-4 in breast milk is derived from dietary phylloquinone. Br J Nutr 2002 87 219–226CrossRefGoogle ScholarPubMed
Thomas, DDKrzykowski, KJEngelke, JA&Groblewski, GEExocrine pancreatic secretion of phospholipid, menaquinone-4, and caveolin-1 in vivo. Biochem Biophys Res Commun 2004 319 974–979CrossRefGoogle ScholarPubMed
Usui, YNishimura, NKobayashi, NOkanone, TKimoto, M&Ozawa, KMeasurement of vitamin K in human liver by gradient elution high-performance liquid chromatography using platinumblack catalyst reduction and fluorometric detection. J Chromatogr 1989 489 291–301CrossRefGoogle Scholar