Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our report presents data on maturation of the vitamin K-dependent carboxylation system in fetal and neonatal rat livers. This system which converts precursors of clotting factors II, VII, IX, X, protein S, and protein C to gamma-carboxylated proteins exhibited low gamma-carboxylation activity before birth. However, around the time of birth there was a sudden increase in all enzyme activities associated with the vitamin K-dependent carboxylation system. In 2-d neonatal rats these activities dropped to levels that were measured in fetal livers whereupon the activities had risen to adult levels in 7-d neonatal rats. However, the activities of the two pathways that provide the carboxylase with reduced vitamin KH2 cofactor were never as high as that measured in maternal livers. It appeared that the pathway which is insensitive to coumarin anticoagulant drugs matures later than the coumarin drug-sensitive pathway. This conclusion is supported by the finding of a late appearance in development of the vitamin K-reducing enzyme DT-diaphorase. Warfarin, when administered to the mother, affected the fetal livers at all stages of development studied (d 16-21). This was clearly demonstrated by vitamin K-dependent 14C-labeling of a 70-kD liver protein that has been shown previously to be a marker for the effect of this drug on the liver. The data demonstrate a similar mechanism of action of warfarin in fetal and neonatal rat livers and an ongoing maturation process of the vitamin K-dependent carboxylation system in these rats.
 ...
PMID:Vitamin K-dependent carboxylation in the developing rat: evidence for a similar mechanism of action of warfarin in fetal and adult livers. 250 52

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.
 ...
PMID:Vitamin K-dependent reactions in rat liver: role of flavoproteins. 731 May 34