Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The nephrotoxicant N-(3,5-dichlorophenyl)succinimide (NDPS) underwent nonenzymatic hydrolysis to N-(3,5-dichlorophenyl)succinamic acid (NDPSA) in buffer, rat liver and kidney homogenates, and rabbit liver homogenates. 2. In the presence of NADPH, rat liver homogenates converted NDPS to NDPSA and N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA). 3. Using liver homogenates from the phenobarbital (PB)-pretreated rat, 2-NDHSA production was increased 5-fold, and the metabolites N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dichlorophenyl)-3-hydroxysuccinamic acid (3NDHSA) were also detected. Formation of these latter metabolites was suppressed by CO or omission of NADPH. No hydroxylated metabolites were detected when NDPSA was incubated with PB-induced rat liver homogenates. 4. Oxidative metabolites were not produced when NDPS was incubated with kidney homogenates from the control or PB-pretreated rat. 5. NDHS underwent rapid hydrolysis in buffer to yield 2-NDHSA and 3-NDHSA. 6. Rabbit liver homogenates converted NDPS to NDPSA, 3,5-dichloroaniline (DCA), and succinic acid (SA). Production of DCA and SA was inhibited by the amidase inhibitor bis-p-nitrophenyl phosphate. Oxidative metabolism did not occur in rabbit tissue. 7. These experiments demonstrate that a PB-inducible form of rat liver P450 converts NDPS to NDHS, which then undergoes hydrolysis to 2-NDHSA and 3-NDHSA. An alternative route of production for 2-NDHSA and 3-NDHSA, via hydroxylation of NDPSA, does not occur. In rabbit liver NDPS metabolism was primarily amidase-mediated.
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PMID:In vitro metabolism of the nephrotoxicant N-(3,5-dichlorophenyl)succinimide in the Fischer 344 rat and New Zealand white rabbit. 917 78

ADAR1 (adenosine deaminase acting on RNA) catalyzes the deamination of adenosine to inosine on RNA substrates with double-stranded character. Here, we show that coexpression of ADAR1 in mammalian cells markedly increases plasmid-based gene expression in transfected cells. The enhanced expression was independent of the nature of the promoter (viral and cellular) used to drive gene expression, of the protein reporter (luciferase and RRP) tested, and of the human cell line examined (293T and HeLa). Exogenous protein levels were increased by approximately 20-fold to approximately 50-fold when ADAR1 was coexpressed, whereas RNA transcript levels changed by less than 2-fold. The activation of PKR (protein kinase regulated by RNA) protein kinase and the phosphorylation of translation initiation factor eIF-2alpha seen following plasmid DNA transfection were both greatly reduced in ADAR1-transfected cells. Stable knockdown of the PKR kinase increased reporter gene expression in the absence, but not in the presence, of ADAR1 coexpression. Both size forms of ADAR1-the p150-inducible form and the p110-like constitutive form-enhanced plasmid-based gene expression. Taken together, these results indicate that the ADAR1 deaminase increases exogenous gene expression at the translational level by decreasing PKR-dependent eIF-2alpha phosphorylation.
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PMID:Adenosine deaminase ADAR1 increases gene expression at the translational level by decreasing protein kinase PKR-dependent eIF-2alpha phosphorylation. 1973 81