Gene/Protein Disease Symptom Drug Enzyme Compound
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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.
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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

Vitamin K is required as a cofactor for a microsomal enzyme that converts glutamyl residues in precursor proteins to gamma-carboxyglutamyl residues in completed proteins. These residues are essential for the biological function of prothrombin, factors VII, IX, and X, protein C, and protein S. Current data suggest that recognition of protein substrates by the carboxylase requires an unidentified protein-protein interaction in addition to the Glu substrate binding site. The primary vitamin K-dependent event has now been shown to be the abstraction of the gamma-hydrogen of the substrate Glu residue with the concurrent formation of vitamin K 2,3-epoxide. Coumarin anticoagulants appear to inhibit the microsomal vitamin K epoxide reductase and one of a number of microsomal quinone reductases. They therefore block vitamin K action by preventing the recycling of vitamin K epoxide to the quinone and to the active cofactor form, the hydroquinone. Excess vitamin K can reverse a coumarin anticoagulant effect as the nonsensitive quinone reductase can continue to furnish the active coenzyme.
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PMID:Studies of the vitamin K-dependent carboxylase and vitamin K epoxide reductase in rat liver. 353 Aug 99

The gamma-carboxyglutamate-containing proteins are a family of secreted vitamin K-dependent proteins in which some glutamyl residues are post-translationally modified to gamma-carboxyglutamic acid residues. A vitamin K-dependent gamma-glutamyl carboxylase enzyme catalyses this post-translational modification. The gamma-carboxylase reaction requires vitamin K in its reduced form, vitamin K hydroquinone, and generates gamma-carboxyglutamate and vitamin K 2,3,-epoxide which is then recycled back to the hydroquinone form by a vitamin K reductase system. Warfarin blocks the vitamin K cycle and hence inhibits the gamma-carboxylase reaction, and this property of Warfarin has led to its wide use in anticoagulant therapy. Until recently, interest in vitamin K-dependent proteins was mostly restricted to the field of hematology. However, the discovery that the anti-coagulant factor protein S and its structural homologue Gas6 (growth arrest-specific gene 6), two vitamin K-dependent proteins, are ligands for the Tyro3/Axl/Mer family of related tyrosine kinase receptors has opened up a new area of research. Moreover, the phenotypes associated with the invalidation of genes encoding vitamin K-dependent proteins or their receptors revealed their implication in regulating phagocytosis during many cell differentiation phenomena such as retinogenesis, neurogenesis, osteogenesis, and spermatogenesis. Additionally, protein S was identified as the major factor responsible for serum-stimulated phagocytosis of apoptotic cells. Therefore, the elucidation of the molecular mechanisms underlying the role of vitamin K-dependent proteins in regulating apoptotic cell phagocytosis may lead to a better understanding of the physiopathology of cell differentiation and could form the framework of new therapeutic strategies aiming at a selective targeting of cell phagocytosis associated pathologies.
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PMID:[Gas-6 and protein S: vitamin K-dependent factors and ligands for the TAM tyrosine kinase receptors family]. 1793 90