Relationship between vitamin K-dependent carboxylation and vitamin K epoxidation.
It has been postulated that the liver microsomal conversion of vitamin K hydroquinone to its 2,3-epoxide (epoxidase activity) is coupled in some obligatory fashion to the vitamin K-dependent carboxylation (carboxylase activity) event also occurring in microsomes. This hypothesis is supported by the observations that the requirements for the two reactions are similar and that conditions that promote increased carboxylation increase the epoxidase activity. It has now been shown that both of these reactions are localized in the rough microsomal fraction of a cellular homogenate, and that both activities appear to be located on the luminal rather than the outer surface of microsomal membrane vesicles. The epoxidase activity has been found to be enriched as the microsomal carboxylase activity is fractionated, and a microsomal inhibitor of the carboxylase activity had been shown to also inhibit the epoxidase activity. The enzyme glutathione peroxidase inhibits both of these activities, suggesting that a hydroperoxide of the vitamin might be an intermediate for both reactions. The organic hydroperoxide t-butyl-OOH has also been shown to have weak vitamin K-like activity in an in vitro system. These data strengthen the hypothesis that these two reactions are related, perhaps through a common intermediate, but do not provide a definite molecular role for this interrelationship.
D015055:1-Carboxyglutamic Acid / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002262:Carboxy-Lyases / Q000378:metabolism; D004852:Epoxy Compounds; D005971:Glutamates / Q000378:metabolism; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D051381:Rats; D014812:Vitamin K / Q000031:analogs & derivatives / Q000502:physiology*
D004852:Epoxy Compounds; D005971:Glutamates; D014812:Vitamin K; D002245:Carbon Dioxide; D015055:1-Carboxyglutamic Acid; D011516:Prothrombin; D010544:Peroxidases; D002262:Carboxy-Lyases