Vitamin K-dependent reactions in rat liver: role of flavoproteins.
The role of flavins in vitamin K function was assessed by examining blood coagulation and in vitro activities of hepatic vitamin K-dependent enzymes from control and riboflavin-deficient rats. One-stage prothrombin times and Factor VII activities were lower in flavin-deficient rats than in ad libitum or pair-fed controls. Fibrinogen, prothrombin, and Factor X activities were normal. Hepatic vitamin K-dependent carboxylase activity was severely depressed in flavin-deficient rats when assayed with [vitamin K + NADH] and somewhat depressed with reduced vitamin K (vitamin KH2) as substrate. One-hour flavin repletion appreciably restored [vitamin K + NADH]-dependent activity, but vitamin KH2-dependent activity was not restored even after 16 hours repletion. These results suggest that the carboxylating enzyme itself is not a flavoprotein, but that the microsomal NADH dehydrogenase required for [vitamin K + NADH]-dependent carboxylation is a flavoprotein. This dehydrogenase may differ from the cytosolic Warfarin-inhibitable 'DT-diaphorase' in that the activity of the latter, which is reduced 50% in flavin-deficient rats, is not at all restored by one-hour flavin repletion. Flavin status-dependent differences in NADH-dependent or vitamin KH2-dependent epoxidation of vitamin K paralleled differences in the carboxylase. Flavin deficiency had no effect on vitamin K 2,3-epoxide reductase activity nor on its inhibition by Warfarin.
D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D002262:Carboxy-Lyases / Q000378:metabolism; D005167:Factor VII / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009245:NADH Dehydrogenase / Q000378:metabolism; D011808:Quinone Reductases / Q000378:metabolism; D051381:Rats; D012256:Riboflavin / Q000494:pharmacology; D012257:Riboflavin Deficiency / Q000503:physiopathology*; D014812:Vitamin K / Q000502:physiology*; D014859:Warfarin / Q000494:pharmacology
D014812:Vitamin K; D014859:Warfarin; D005167:Factor VII; D011808:Quinone Reductases; D009245:NADH Dehydrogenase; D002262:Carboxy-Lyases; D012256:Riboflavin