Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.1 (NADPH-diaphorase)
 3,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

N-acetylcysteine (NAC) is often administered to respiratory patients with histories of exposure to noxious agents (e.g. cigarette smoke and atmospheric pollutants), which are known to act as glutathione (GSH) depletors and as cancer initiators and/or promoters. Since NAC is a precursor of intracellular GSH, we investigated its effects on GSH metabolism and on the biotransformation of carcinogenic and/or mutagenic compounds. In vitro, NAC induced a significant increase in oxidized glutathione (GSSG) reductase activity in rat liver preparations and counteracted the mutagenicity of direct-acting compounds (such as epichlorohydrin, hydrogen peroxide, 4-nitroquinoline-N-oxide and dichromate), as a result of its reducing and scavenging properties. At high concentrations, the drug completely inhibited the mutagenicity of procarcinogens (cigarette smoke condensate, tryptophan pyrolysate, cyclophosphamide, 2-aminofluorene, benzo(a)pyrene and aflatoxin B1) by binding their electrophilic metabolites. In contrast, their metabolic activation was stimulated by decreasing NAC concentrations, especially when liver preparations from enzyme-induced rats were used. Lung and liver subcellular preparations of rats treated in vivo with NAC, in various combinations with enzyme inducers and/or GSH depletors, also affected the mutagenicity of a number of compounds. NAC generally increased intracellular GSH and restored its levels following depletion. It did not affect the levels nor the spectral properties of cytochromes P-450 in pulmonary and hepatic microsomes, whereas it stimulated, especially in Aroclor-pretreated animals, cytosolic enzyme activities involved in NADP or GSSG reduction (G6PD, 6PGD and GSSG reductase) and in the reductive detoxification of xenobiotics (DT diaphorase). When administered with the diet, at a nontoxic posology (120 mg/kg b.w.), NAC markedly inhibited the induction of lung tumors in mice by a potent carcinogen (urethane).
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PMID:Metabolic, desmutagenic and anticarcinogenic effects of N-acetylcysteine. 380 42

Extracts of E. coli contain at least three easily separable NAD(P)H:paraquat diaphorases. One of these is identified as thioredoxin reductase, which accounts for most of the PQ++ diaphorase in a thioredoxin reductase overproducer but is only 25% of this activity in a wild type. NADP+, but not NAD+, inhibited the diaphorase activity of thioredoxin reductase. All of the soluble PQ++ diaphorases of E. coli are stable during fractionation by HPLC and none depend upon the cooperative action of components separable by this technique. GSSG reductase is inhibited by PQ++ and is not, to any significant degree, a contributor to the diaphorase activity of E. coli.
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PMID:Paraquat diaphorases in Escherichia coli. 802 98