Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of phenytoin (DPH) on folate metabolism have been studied in female Swiss Webster mice. Doses of DPH which produce steady-state plasma levels of DPH in the therapeutic range of 10-20 micrograms/ml were found to decrease plasma folate levels. In addition, the in vivo oxidation rate of [14C] formate and [2-14C] histidine to 14CO2 was increased. The increased metabolic rates were accompanied by a decrease in the hepatic activity of N5, N10-methylenetetrahydrofolate (5, 10-CH2-H4folate) reductase. N5-methyltetrahydrofolate-homocysteine transmethylase (methionine synthase); EC 2.1.1.13) activity in the liver was unchanged. The distribution of folates in the liver was determined by high-pressure liquid chromatography (HPLC) and it was found that the concentration of tetrahydrofolate (H4folate) was increased in DPH-treated mice whereas the concentration of N5-methyltetrahydrofolate was decreased. These effects were observed in mice treated with DPH for 4 days, but not in mice given a single DPH injection 24 hr previously. Decreased activity of hepatic 5, 10-CH2-H4folate reductase is postulated to account for the other effects which were observed. Decreased activity presumably results in increased tissue concentrations of 5, 10-CH2-H4folate, which is in equilibrium with its dissociation products, H4folate and formaldehyde. Increased concentrations of H4folate lead to increases in the oxidation rate of formate and histidine. These effects on folate metabolism may have important implications in the pharmacological and toxicological effects of DPH.
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PMID:Decreased hepatic 5, 10-methylenetetrahydrofolate reductase activity in mice after chronic phenytoin treatment. 637 25

A flock of Rambouillet sheep was examined because of increased lamb mortality caused by ineffective hemostasis at parturition. Neonatal-affected lambs presented with inadequate hemostasis at the umbilicus, pale mucus membranes, and markedly prolonged activated clotting time. Affected lambs had consistently prolonged 1-stage prothrombin times and activated partial thromboplastin times that supported a defect in the common pathway or defects in both the intrinsic and extrinsic pathway of the coagulation cascade. Decreased activity of vitamin K-dependent procoagulant factors II, VII, IX, and X in male and female lambs suggested either a defect of the hepatic enzyme gamma-glutamyl carboxylase, or vitamin K(1) 2,3 epoxide reductase. Affected lamb hepatic gamma-glutamyl carboxylase activity was markedly decreased compared with that of age- and sex-matched control lambs, while vitamin K(1) 2,3 epoxide reductase and glucose-6-phosphatase activities were similar between an affected and normal lamb. Subcutaneous vitamin K(1) supplementation did not increase vitamin K-dependent procoagulant factor activities in 3 lambs administered vitamin K(1) daily. These data confirm defective gamma-glutamyl carboxylase activity as the cause of impaired coagulation of sheep in this flock. This flock represents the only viable animal model of hereditarily defective gamma-glutamyl carboxylase activity.
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PMID:Defective gamma-glutamyl carboxylase activity and bleeding in Rambouillet sheep. 1696 51

S-nitrosoglutathione reductase (GSNOR) reduces the nitric oxide (NO) adduct S-nitrosoglutathione (GSNO), an essential reservoir for NO bioactivity. In plants, GSNOR has been found to be important in resistance to bacterial and fungal pathogens, but whether it is also involved in plant-herbivore interactions was not known. Using a virus-induced gene silencing (VIGS) system, the activity of GSNOR in a wild tobacco species, Nicotiana attenuata, was knocked down and the function of GSNOR in defence against the insect herbivore Manduca sexta was examined. Silencing GSNOR decreased the herbivory-induced accumulation of jasmonic acid (JA) and ethylene, two important phytohormones regulating plant defence levels, without compromising the activity of two mitogen-activated protein kinases (MAPKs), salicylic acid-induced protein kinase (SIPK) and wound-induced protein kinase (WIPK). Decreased activity of trypsin proteinase inhibitors (TPIs) were detected in GSNOR-silenced plants after simulated M. sexta feeding and bioassays indicated that GSNOR-silenced plants have elevated susceptibility to M. sexta attack. Furthermore, GSNOR is required for methyl jasmonate (MeJA)-induced accumulation of defence-related secondary metabolites (TPI, caffeoylputrescine, and diterpene glycosides) but is not needed for the transcriptional regulation of JAZ3 (jasmonate ZIM-domain 3) and TD (threonine deaminase), indicating that GSNOR mediates certain but not all jasmonate-inducible responses. This work highlights the important role of GSNOR in plant resistance to herbivory and jasmonate signalling and suggests the potential involvement of NO in plant-herbivore interactions. Our data also suggest that GSNOR could be a target of genetic modification for improving crop resistance to herbivores.
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PMID:S-Nitrosoglutathione reductase (GSNOR) mediates the biosynthesis of jasmonic acid and ethylene induced by feeding of the insect herbivore Manduca sexta and is important for jasmonate-elicited responses in Nicotiana attenuata. 2162 39