Natural prenylquinones inhibit the enzymes of the vitamin K cycle in vitro

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.