Co-purification of microsomal epoxide hydrolase with the warfarin-sensitive vitamin K1 oxide reductase of the vitamin K cycle

Biochemical Pharmacology
T M GuenthnerReidar Wallin

Abstract

Vitamin K1 oxide reductase activity has been partially purified from rat liver microsomes. A three-step procedure produced a preparation in which warfarin-sensitive vitamin K1 oxide reductase activity was 118-fold enriched over the activity in intact rat liver microsomes. A major component of the multi-protein mixture was identified as a 50 kDa protein that strongly cross-reacts with antiserum prepared against homogeneous rat liver microsomal epoxide hydrolase. The reductase preparation also had a high level or epoxide hydrolase activity against two xenobiotic epoxide substrates. The K(m) values for hydrolysis by the reductase preparation were similar to those for homogeneous microsomal epoxide hydrolase itself, and the specific hydrolase activities of the reductase preparation were 25-35% of the specific activities measured for the homogeneous hydrolase preparation. Antibodies prepared against homogeneous microsomal epoxide hydrolase inhibited up to 80% of reductase activity of the reductase preparation. Homogeneous microsomal epoxide hydrolase had no vitamin K1 oxide reductase activity. This evidence suggests that microsomal epoxide hydrolase, or a protein that is very similar to it, is a major functional component of a multi...Continue Reading

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Citations

Jun 20, 2001·Clinica Chimica Acta; International Journal of Clinical Chemistry·M W Linder
Sep 20, 2006·The Pharmacogenomics Journal·M Wadelius, M Pirmohamed
Dec 15, 2015·Journal of Thrombosis and Haemostasis : JTH·J-K Tie, D W Stafford
Feb 7, 2012·Toxicology and Applied Pharmacology·Hongying DuanToshitaka Akatsuka
Aug 17, 2005·Journal of Thrombosis and Haemostasis : JTH·D W Stafford
Sep 25, 2007·Chemistry & Biodiversity·Bernard Testa, Stefanie D Krämer
Nov 13, 2004·Chemico-biological Interactions·Vinayak P HosagraharaCurtis J Omiecinski
Jun 25, 2014·Journal of Lipid Research·Kasem NithipatikomWilliam B Campbell
May 15, 2007·The Journal of Pharmacology and Experimental Therapeutics·Evgeny Krynetskiy, Patrick McDonnell
Dec 31, 2020·International Journal of Molecular Sciences·Jérémie Gautheron, Isabelle Jéru

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