Disease relevance of Cyb5r3

• While X-ray structures have been determined for the soluble, flavin-containing diaphorase domains of the rat and pig enzymes, no X-ray or NMR structure has been described for the human enzyme or any of the methemoglobinemia variants [1].
• Extra-hepatic Walker sarcoma 256 produced a marked decrease (approximately 60%) in the levels of cytochrome P-450 and NADP-cytochrome P-450 reductase in rat liver endoplasmic reticulum, and a lesser decrease (approximately 20%) of cytochrome b5 and NADH-cytochrome b5 reductase [2].
• This study determined the presence of nitric oxide synthase in the brain stem circuit controlling esophageal peristalsis by combining transsynaptic retrograde tract tracing with pseudorabies virus and nicotinamide adenine dinucleotide phosphate diaphorase (NADPH) histochemistry [3].
• METHODS: Acute colitis in rats was induced with 5% acetic acid. iNOS messenger RNA (mRNA) was analyzed by Northern analysis, and reduced nicotinamide adenine dinucleotide phosphate diaphorase was used to identify potential NO synthase activity [4].
• In newborn rats and in rats with regenerative hyperplasia following wounding of the urothelium, the diaphorase staining was less than that in the untreated adult [5].

Psychiatry related information on Cyb5r3

• Neurons containing reduced nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase and acetylcholinesterase in the striatum are spared in Huntington's disease [6].

High impact information on Cyb5r3

• Reduced nicotinamide adenine dinucleotide phosphate diaphorase localized NO synthase activity to MPNs in controls and in epithelial cells and MPNs in the inflamed colon [4].
• Manganese superoxide dismutase and reduced nicotinamide adenine dinucleotide diaphorase colocalize in the rat gut [7].
• Mn SOD is colocalized with reduced nicotinamide adenine dinucleotide (NADH) diaphorase in some tissues [7].
• Reduced nicotinamide adenine dinucleotide phosphate diaphorase staining showed increased centrilobular staining of hepatocytes in the corn oil and ethanol group and L-NAME-treated group [8].
• NADH diaphorase histochemistry (with Triton X-100) resulted in identical staining [7].

Chemical compound and disease context of Cyb5r3

• Nicotinamide adenine dinucleotide phosphate diaphorase histochemistry generally stained cells of similar distribution but did reveal somewhat more extensive localizations in peripheral ocular tissues, the ciliary ganglion, and the retina, compared with nitric oxide synthase immunohistochemistry [9].
• Experimental hepatomas: dehydrogenation of reduced pyridine nucleotides by the D-T diaphorase [10].
• The results are interpreted as indicating that the myositis in addition to the surgical operations represents a supramaximal input to the dorsal horn causing neurotoxic effects in diaphorase- positive neurones [11].
• In the present experiments, the effect of alterations in tissue diaphorase activities on the toxicity of a third naphthoquinone derivative, 2,3-dimethyl-1,4-naphthoquinone, has been investigated [12].

Biological context of Cyb5r3

• Heterogeneity of the rat NADH-cytochrome-b5-reductase transcripts resulting from multiple alternative first exons [13].
• This model of gene expression in rat could be important in understanding the basis for the different types of the NADH-cytochrome-b5-reductase enzyme and their deficiency in man [13].
• Rat cDNA encoding NADH-cytochrome b5 reductase (b5R) was isolated from a rat liver cDNA library using a human b5R cDNA as a probe [14].
• The reducing ability of iron chelates by NADH-cytochrome B5 reductase or cytochrome B5 responsible for NADH-supported lipid peroxidation [15].
• The three purified proteins which are required for microsomal stearyl-CoA desaturation, NADH-cytochrome b5 reductase, cytochrome b5, and desaturase, have been combined with egg lecithin or dimyristyl lecithin vesicles to reconstruct a functional electron transport system capable of utilizing NADH and O2 in the desaturation of stearyl-CoA [16].

Anatomical context of Cyb5r3

• Detergent-solubilized NADH-cytochrome b5 reductase was purified from human liver microsomes [17].
• These results indicate that NADH-cytochrome b5 reductase is an authentic component of Golgi membranes, as well as of microsomes and of mitochondria [18].
• The subcellular distribution of NADH-cytochrome b5 reductase in rat liver cells was reinvestigated [18].
• Rat erythrocyte NADH-cytochrome b5 reductase. Quantitation and comparison between the membrane-bound and soluble forms using an antibody against the rat liver enzyme [19].
• The ATP-dependent proteolytic system present in reticulocytes can release the active hydrophilic domain of cytochrome b5 and NADH-cytochrome b5 reductase from the endoplasmic reticulum, that in mature erythrocytes act as methemoglobin reductase [20].

Associations of Cyb5r3 with chemical compounds

• Posttranslational iron insertion into the apoproteins, either in vitro with membrane preparations or by iron addition during induction, results in the formation of active holoenzyme which can be reconstituted with NADH cytochrome b5 reductase and cytochrome b5 to form an active stearyl-CoA desaturase system [21].
• The reoxidation of cytochrome b5, after exhaustion of NADH, precedes that of cytochrome c. NADH oxidation is blocked by mersalyl, an inhibitor of NADH-cytochrome b5 reductase [22].
• Isolated and purified microsomal NADH-cytochrome b5 reductase (EC 1.6.2.2) was incubated with bleomycin (BLM) and FeCl3 in the presence of NADH [23].
• Mercuric chloride and p-chloromercuriphenylsulfonate, inhibitors on NADH-cytochrome b5 reductase, at 32 microM inhibited NADH-supported palmitoyl-CoA elongation to 30 and 60% of control activity, respectively, whereas NADPH-supported palmitoyl-CoA elongation was unaffected by these mercurials [24].
• The use of antibodies against NADPH-cytochrome P-450 reductase, NADH-cytochrome b5 reductase and cytochrome b5 demonstrated that both the NADH- and the NADPH-supported reactions depend on established components of cytochrome P-450 systems [25].

Enzymatic interactions of Cyb5r3

• NADPH-cytochrome P450 reductase catalyzed orthovanadate-dependent NADPH oxidation five times faster than NADH-cytochrome b5 reductase catalyzed NADH oxidation [26].

Regulatory relationships of Cyb5r3

• NADH-supported reduction of cytochrome b5 was also inhibited by propylthiouracil in the reconstituted system consisting of cytochrome b5 and partially purified NADH-cytochrome b5 reductase [27].
• Our data identify copper complexes with SOD mimicking activity as a novel class of neuronal NOS inhibitors blocking the reductase (diaphorase) activity of the enzyme [28].
• Structural and functional analogs of CuZn superoxide dismutase inhibit rat brain nitric oxide synthase by interference with the reductase (diaphorase) domain [28].

Other interactions of Cyb5r3

• The results showed the selectivity of NADH-cytochrome b5 reductase or cytochrome b5 towards iron chelates and the subsequent ability of this system to promote peroxidation [15].
• The subcellular distribution of rat erythrocyte NADH-cytochrome b5 reductase was determined by radioimmunoassay, using a rabbit antibody against the cathepsin D cleaved water-soluble fragment of rat liver microsomal reductase (I-reductase), which is known to be immunologically similar to the red cell enzyme [19].
• Cytochrome P-450, NADPH-cytochrome P-450 reductase and cytochrome b5 levels were also unchanged, while slight increases were detected in NADH-cytochrome b5 reductase and epoxide hydrase activities [29].
• Indomethacin in vitro also caused a loss of cytochrome b5, NADH-cytochrome b5 reductase, NADPH-cytochrome c reductase and epoxide hydrolase activities, but an activation of UDP-glucuronyltransferase [30].
• (2) Plasma membrane, Golgi apparatus, and nuclear membrane fractions had relatively high epoxide hydrolase and NADH-cytochrome b5 reductase activities as well as high concentrations of cytochromes b5 and P-450 (20-30% of levels present in smooth ER on a phospholipid basis) [31].

Analytical, diagnostic and therapeutic context of Cyb5r3

• Molecular cloning of a cDNA encoding rat NADH-cytochrome b5 reductase and the corresponding gene [14].
• When rats were fed the sunflower oil diet, the cytochrome P-450 concentration and NADH-cytochrome-b5 reductase activity at 120 days were, respectively, 11 and 23% lesser than those of control group [32].
• Immunocytochemistry, in situ hybridisation, nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemistry, and ethidium bromide staining were used to investigate the number of enteric neurones expressing neuropeptides and nitric oxide synthase, and the frequency of ICC [33].
• Urinary NO production was measured, and levels and activity of the different NOS isoforms were determined by a combination of techniques, including immunoblotting, immunohistochemistry, diaphorase staining, and reverse transcription-polymerase chain reaction [34].
• Site-directed mutagenesis has been used to engineer the soluble rat cytochrome b(5) reductase diaphorase domain to utilize NADPH as the preferred electron donor [35].

References