Disease relevance of Por

• The structure of rat liver CPR, expressed in Escherichia coli and solubilized by limited trypsinolysis, has been determined by x-ray crystallography at 2.6 A resolution [1].
• Transient cotransfection of P450R promoter/chloramphenicol acetyl transferase (CAT) constructs and the thyroid hormone receptor beta1 (TR beta1) expression plasmid into rat hepatoma H4IIE cells resulted in a 2.4-fold induction of promoter activity that was both T3 and TR beta1 dependent [2].
• The interaction of paraquat with NADPH-cytochrome P-450 reductase and ferric complexes resulted in an increase in oxygen radical generation, and various ferric complexes increased the catalytic effectiveness and potentiated significantly the toxicity of paraquat via this synergistic increase in oxygen radical generation by the reductase [3].
• Here we investigate the effects of T3-induced hyperthyroidism on the regulation of P450R protein synthesis [4].
• NADPH-cytochrome P450 reductase activity and cytochrome P450 content were decreased by ischemia/reperfusion [5].

High impact information on Por

• The enzyme system consists of a lipid fraction (phosphatidylcholine), cytochrome P450 and NADPH-cytochrome P450 reductase [6].
• Enzyme expression in the periportal region was not affected, but the pericentral rim of hepatocytes expressing glutamine synthetase, ornithine aminotransferase, and NADPH cytochrome P-450 reductase (CYPred) first declined in diameter, then became discontinuous, and finally disappeared [7].
• In rats fed commercial chow diet, cytochrome P-450 content and drug-metabolizing enzyme activity in villous tip cells of duodenal mucosa were higher than in animals fed a semisynthetic diet, but cytochrome b5 and NADPH-cytochrome P-450 reductase were unaffected [8].
• Activities of benzpyrene hydroxylase, p-nitroanisole O-demethylase, and NADPH-cytochrome P-450 reductase and cytochrome P-450 content were 3 to 10 times higher in epithelial cells of the upper villus than in mucosal crypt cells [8].
• We have investigated the sites of N-terminally truncated cytochrome P4501A1 targeted to mitochondria (P450MT2) which interact with adrenodoxin (Adx), cytochrome P450 reductase (CPR) and bacterial flavodoxin (Fln) [9].

Chemical compound and disease context of Por

• Fao hepatoma cells, where CYP2E1 showed a half-life of 4 h upon serum withdrawal, were treated for 1 h with 0.3 microM diphenylene iodonium (DPI), a suicide inhibitor of flavoenzymes, which resulted in approximately 90% inhibition of the microsomal NADPH-cytochrome P450 reductase and CYP2E1-dependent chlorzoxazone hydroxylase activities [10].
• Hyperthyroidism elicited a calorigenic response and increased specific and molecular activities of NADPH-cytochrome P450 reductase, O2.- generation, and G-6PDH activity, concomitantly with diminution in liver SOD and catalase activities and in alpha-tocopherol, beta-carotene, and lycopene levels [11].
• NADPH-cytochrome P-450 reductase was purified to homogeneity from hepatoma 5123t.c.(H) microsomes from phenobarbital and hydrocortisone-treated rats by detergent solubilization and affinity chromatography with an overall 8% recovery [12].

Biological context of Por

• These results indicated that a functional electron-transport chain consisting of rat NADPH-cytochrome P-450 reductase and rat cytochrome P-450MC was constructed in S. cerevisiae cells [13].
• Similarities in amino acid sequence and in functional domain arrangement with other key flavoproteins, including nitric oxide synthase, make CPR an excellent prototype for studies of interactions between two flavin cofactors [14].
• On the other hand, Lys(149) is close to a cluster of acidic amino acids near the FMN binding site of CPR [15].
• Alkylation of cytochrome P-450c with BrNAP markedly stimulated (approximately 30-fold) its rate of anaerobic reduction by NADPH-cytochrome P-450 reductase, as determined by stopped flow spectroscopy [16].
• The gene coding for the Candida tropicalis NADPH-cytochrome P-450 oxidoreductase (CPR, NADPH: ferricytochrome oxidoreductase, EC 1.6.2.4) was isolated by immunoscreening of a C. tropicalis lambda gt11 expression library and colony hybridization of a C. tropicalis genomic library [17].

Anatomical context of Por

• Presence of NADPH-cytochrome P-450 reductase in rat liver Golgi membranes. Evidence obtained by immunoadsorption method [18].
• We have investigated the degradation in rat liver of two typical endoplasmic reticulum (ER) membrane proteins, phenobarbital (PB)-inducible cytochrome P-450 (P-450[PB]) and NADPH-cytochrome P-450 reductase (FP2) [19].
• The reductase activity could be reconstituted by NADPH-cytochrome P-450 reductase and forms of cytochrome P-450 purified from liver microsomes of polychlorinated biphenyl-induced rats [20].
• The staining for NADPH-cytochrome P-450 reductase was more uniformly distributed within the epithelium than was the cytochrome P-450 BNF-B2-like immunoreactivity [21].
• Purified NADPH cytochrome P-450 reductase. Interaction with hepatic microsomes and phospholipid vesicles [22].

Associations of Por with chemical compounds

• CPR is a membrane-bound protein and catalyzes electron transfer from NADPH to all known microsomal cytochromes P450 [1].
• Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes [1].
• A full-length cDNA for rat NADPH-cytochrome P-450 reductase was cloned by the procedure of Okayama and Berg (1982) from hepatic poly(A)RNA prepared from phenobarbital-induced rats [13].
• Activities of CYP1A2, NADPH-cytochrome P450 reductase, and glutathione S-transferase remained unchanged under these conditions [23].
• NADPH cytochrome P-450 reductase activation of quinone anticancer agents to free radicals [24].

Physical interactions of Por

• An enzymatically active chimeric protein containing the hydrophilic form of NADPH-cytochrome P450 reductase fused to the membrane-binding domain of cytochrome b5 [25].

Enzymatic interactions of Por

• The stimulatory effect of cytochrome b5 on the P-450(1)-catalyzed monooxygenase reactions can be explained by assuming that the rate of the second electron supply to the oxygenated P-450(1)-substrate complex from cytochrome b5 is higher than that directly from NADPH-cytochrome P-450 reductase [26].
• The presence of manganese in the incubation mixture was found to increase the prooxidant role of catalase on autoxidation during one-electron reduction of aminochrome catalyzed by NADPH cytochrome P450 reductase [27].
• A marked difference in the inhibitory effect of superoxide dismutase on oxygen consumption during adrenochrome reduction catalyzed by NADPH-cytochrome P450 reductase and DT-diaphorase was also observed [27].
• NADPH-cytochrome P450 reductase catalyzed orthovanadate-dependent NADPH oxidation five times faster than NADH-cytochrome b5 reductase catalyzed NADH oxidation [28].

Regulatory relationships of Por

• Superoxide dismutase and catalase enhance autoxidation during one-electron reduction of aminochrome by NADPH-cytochrome P-450 reductase [29].
• 1. The t-butylquinone metabolite of BHA was shown to redox cycle with NADPH-cytochrome P-450 reductase leading to enhanced NADPH-oxidase activity for both the purified and liver microsome-bound flavoprotein [30].
• All treatments except 3,4-TBB induced NADPH-cytochrome P-450 reductase and aminopyrine-N-demethylase activities while all treatments except 2,4,5-HBB induced ethoxyresorufin-O-deethylase and UDP-glucuronosyltransferase activities [31].

Other interactions of Por

• The present investigation also reveals that DT-diaphorase and NADPH-cytochrome P-450 reductase can both catalyze the reduction of BP-3,6-quinone for the formation of BP-3,6-quinol glucuronides [32].
• In a low but physiological concentration of NADPH-cytochrome P-450 reductase and excess amount of progesterone, outer mitochondrial membrane cytochrome b5 stimulated the cytochrome P-45017alpha-catalyzed reactions, 17alpha-hydroxylation and C17-C20 bond cleavage [33].
• Heme oxygenase, catalyses oxidation of the heme molecule in concert with NADPH-cytochrome P450 reductase and then specifically cleaves heme into biliverdin, carbon monoxide, and iron [34].
• Similar observations were made with the liver and adrenal HO-2 and the NADPH-cytochrome P-450 reductase of treated rats [35].
• Experiments employing catalase, superoxide dismutase, and NADPH-cytochrome P450 reductase, confirm the previously deduced conclusions from high drug concentrations, that is, that at low concentrations, AZQ acts to shuttle reducing equivalents from the enzyme to oxygen, thus generating the redox cycle [36].

Analytical, diagnostic and therapeutic context of Por

• Por both hormones, when elevations in AP were allowed, marked and roughly proportional increases in the resistance to blood flow through single afferent and efferent arterioles occurred, whereas when increases in AP were prevented by partial aortic constriction increases in resistance were confined primarily to the efferent arteriole [37].
• Crystallization and preliminary x-ray studies of NADPH-cytochrome P450 reductase [14].
• The increase in NADPH-cytochrome P-450 reductase content of liver microsomes prepared from rats either fed or treated i.p. with DHEA was also observed by Western blotting techniques [38].
• Various spectrophotometric titrations were performed to examine the electron-accepting properties of the purified NADPH-cytochrome P-450 reductase and, in particular, to determine the oxidation state of the stable semiquinone form produced by air oxidation of NADPH-reduced enzyme [39].
• Cross-linking of NADPH-cytochrome P-450 reductase by antireductase IgG resulted in complete immobilization of cytochrome P-450 in L/P450 = 1 vesicles [40].

References