Tissue distribution and warfarin sensitivity of vitamin K epoxide reductase.
The distribution of vitamin K epoxide reductase activity and its sensitivity to warfarin have been examined in whole microsomes from tissues of both control and warfarin-resistant strain rats. The distribution of activity roughly paralleled that previously shown for the vitamin K-dependent carboxylase. Activity on a per gram tissue basis was highest in kidney, adrenal, spleen, lung, testes, and epididymis at a level about 1/20th of that present in liver microsomes. Vitamin K quinone formation by microsomes from warfarin-resistant rats was approximately half that of control strain samples. In addition, hydroxy vitamin K was formed by warfarin-resistant strain microsomes to about the same extent as vitamin K quinone in all tissues. The Km values for dithiothreitol (DTT) and vitamin K epoxide were similar in all tissues (range = 0.1-0.2 mM DTT at 40 microM vitamin K epoxide, and 10-30 microM vitamin K epoxide at 2 mM DTT). The sensitivities to warfarin were similar for all control strain rat tissues (I50 = 10-20 microM at 2 mM DTT and 40 microM vitamin K epoxide) and similarly elevated for all warfarin-resistant rat tissues (I50 = 30 to greater than 80 microM). These results suggest that the identical enzyme is expressed in all tissues and that tissue specific isozymes do not occur.
Hazelett
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SE
Department of Chemistry, University of Akron, OH 44325.
Preusch
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PC
D000818:Animals; D004229:Dithiothreitol / Q000494:pharmacology; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D051381:Rats; D013379:Substrate Specificity; D014018:Tissue Distribution; D010837:Vitamin K 1 / Q000031:analogs & derivatives / Q000494:pharmacology; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000494:pharmacology*
C016186:vitamin K1 oxide; D014859:Warfarin; D010837:Vitamin K 1; D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases; D004229:Dithiothreitol