The in vivo effects of oral anticoagulant therapy with 4-hydroxycoumarins on various vitamin K-dependent enzyme systems in man were compared. In hepatic microsomes obtained from donors who has been treated with 4-hydroxycoumarins for more than 6 months, the vitamin K 2,3 epoxide reductase activity and the DTT-dependent vitamin K quinone reductase activity were diminished to 35% and 20% of the corresponding normal values. In the non-hepatic tissues, only a small decrease in vitamin K 2,3 epoxide reductase activity could be demonstrated, while no differences were found in the vitamin K quinone reductase activities. In none of the tissues a significant increase of noncarboxylated precursor proteins was observed, whereas also vitamin K hydroquinone-dependent carboxylase activities seemed to be unaffected by the anticoagulant treatment.
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