title: Natural prenylquinones inhibit the enzymes of the vitamin K cycle in vitro.
abstract: Vitamin K belongs to a class of compounds commonly known as prenylquinones. Three other prenylquinones which are abundantly found in food are plastoquinone-9, ubiquinone-9 and ubiquinone-10. Using in vitro assay systems, it was recently found that synthetic derivatives of prenylquinones inhibit the vitamin K-dependent enzyme gamma-glutamylcarboxylase and, to a lesser extent, the vitamin K-epoxide reductase. In this paper we describe how natural prenylquinones affect the vitamin K-dependent enzymes in vitro. All three prenylquinones were found to inhibit both the vitamin K-dependent carboxylase and the K-epoxide reductase in a rat as well as in a cow liver system; 50% inhibition was obtained at concentrations in the micromolar range. On the basis of their respective standard redox potentials, a possible mechanism for the inhibitory effect of prenylquinones on the carboxylase enzyme is put forward. It is concluded that natural prenylquinones are potential antagonists of vitamin K and may interfere with vitamin K-dependent reactions in vivo.
authors.affiliation: Department of Biochemistry, University of Limburg, Maastricht, The Netherlands.
authors.forename: J E
authors.initials: JE
authors.lastname: Ronden
authors.forename: B A
authors.initials: BA
authors.lastname: Soute
authors.forename: H H
authors.initials: HH
authors.lastname: Thijssen
authors.forename: J
authors.initials: J
authors.lastname: Saupe
authors.forename: C
authors.initials: C
authors.lastname: Vermeer
mesh_terms: D000818:Animals; D019735:Carbon-Carbon Ligases; D002417:Cattle; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006873:Hydroquinones / Q000378:metabolism; D008025:Ligases / Q000037:antagonists & inhibitors; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010944:Plants / Q000737:chemistry; D010971:Plastoquinone / Q000031:analogs & derivatives / Q000494:pharmacology; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology; D014812:Vitamin K / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010837:Vitamin K 1 / Q000031:analogs & derivatives / Q000378:metabolism; D064417:Vitamin K Epoxide Reductases
chemical_list: D004791:Enzyme Inhibitors; D006873:Hydroquinones; D011809:Quinones; D014812:Vitamin K; D014451:Ubiquinone; C016186:vitamin K1 oxide; D010837:Vitamin K 1; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase; D010971:Plastoquinone