Metabolism of vitamin K and prothrombin synthesis: anticoagulants and the vitamin K--epoxide cycle.
Vitamin K is primarily located in hepatic microsomes, where the vitamin K-dependent carboxylation in prothrombin synthesis occurs. Recent evidence supports the idea that the carboxylation is linked to the metabolism of the vitamin--specifically the cyclic interconversion of vitamin K and vitamin K epoxide. The primary site of action of coumarin and indandione anticoagulants appears to be an inhibition of the epoxide-to-vitamin K conversion in this cycle. There is a correlation between the inhibition of prothrombin synthesis and the regeneration of vitamin K from the epoxide by anticoagulants. In hamsters and warfarin-resistant rats prothrombin synthesis and the epoxide-K conversion are less sensitive to warfarin than in the normal rat. The epoxide-K conversion is impaired in resistant rats, which may explain their high vitamin K requirement. There is also a correlation between vitamin K epoxidation and vitamin K-dependent carboxylation, but the apparent link may be because vitamin K hydroquinone is an intermediate in the formation of the epoxide and also the active form in carboxylation. The vitamin K-epoxide cycle is found in extrahepatic tissues such as kidney, spleen, and lung and is inhibited by warfarin.
D015055:1-Carboxyglutamic Acid / Q000378:metabolism; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D006224:Cricetinae; D004351:Drug Resistance; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004852:Epoxy Compounds; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors; D011516:Prothrombin / Q000096:biosynthesis*; D051381:Rats; D014812:Vitamin K / Q000031:analogs & derivatives / Q000378:metabolism*; D010837:Vitamin K 1 / Q000031:analogs & derivatives
D000925:Anticoagulants; D004852:Epoxy Compounds; D014812:Vitamin K; C016186:vitamin K1 oxide; D015055:1-Carboxyglutamic Acid; D010837:Vitamin K 1; D011516:Prothrombin; D010088:Oxidoreductases