Stereospecificity of vitamin K-epoxide reductase.
Vitamin K epoxide can occur as a pair of optical isomers due to the asymmetry of the oxirane ring substituents. The stereoselectivity of vitamin K-epoxide reductase for the oxirane ring configuration was determined by recovery of the partially resolved unreacted substrate following incubations of racemic vitamin K epoxide with rat liver microsomes. The substrate ws enriched for the (--)-enantiomer, but selectivity for the biologically relevant (+)-enantiomer was low. This result was confirmed by direct comparison of the rates of reaction for the racemic substrate and (+)-vitamin K epoxide. The selectivity of vitamin K-epoxide reductase for the cis- or trans-phytyl configuration of the vitamin K side chain was also low. These results suggest an enzyme-active site which is open toward the 2,3-positions and is able to bind the substrate in two opposite orientations with respect to the positions of the methyl and phytyl side chain substituents.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism; D013379:Substrate Specificity; D064417:Vitamin K Epoxide Reductases
D006899:Mixed Function Oxygenases; D064417:Vitamin K Epoxide Reductases