Vitamin K epoxide and quinone reductase activities. Evidence for reduction by a common enzyme.
Vitamin K hydroquinone formation in rat liver can be catalyzed by a thiol-dependent quinone reductase activity which shares several characteristics with the vitamin K 2,3-epoxide reductase activity. The possibility that a single enzyme catalyzes both reductions was investigated. Values of Vmax/Km for several different vitamin K analogs were determined and found to be similar for both reductase activities. Several different coumarins were also shown to achieve 50% inhibition at similar concentrations for both enzyme activities. The chloro analog of menaquinone-2 was shown to inhibit both reductases, and the presence of either the quinone or epoxide form of the vitamin protected both activities from inactivation. Thioredoxin was shown to function as a reductant for both reductase activities, although the maximum enzyme activity achieved by this reductant was only half that achieved with dithiothreitol as a reductant. Cofractionation of the two reductase activities on a variety of column matrices was also observed. These data strongly support the hypothesis that one microsomal enzyme is capable of catalyzing both reduction of vitamin K 2,3-epoxide to the quinone, and the quinone to vitamin K hydroquinone.
Gardill
S L
SL
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison 53706.
Suttie
J W
JW
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D007700:Kinetics; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D011808:Quinone Reductases / Q000378:metabolism*; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity; D013879:Thioredoxins / Q000494:pharmacology; D014812:Vitamin K / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism*; D010837:Vitamin K 1 / Q000031:analogs & derivatives* / Q000378:metabolism
D011809:Quinones; D014812:Vitamin K; C016186:vitamin K1 oxide; D013879:Thioredoxins; D010837:Vitamin K 1; D011808:Quinone Reductases