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

We have engineered an industrial strain of the yeast, Candida tropicalis, for the efficient production of long-chain dicarboxylic acids, which are important raw materials for the chemical industry. By sequential disruption of the four genes encoding both isozymes of the acyl-CoA oxidase which catalyzes the first reaction in the beta-oxidation pathway, alkane and fatty acid substrates have been successfully redirected to the omega-oxidation pathway. Consequently, the conversion efficiency and chemical selectivity of their terminal oxidation to the corresponding dicarboxylic acids has been improved to 100 percent. The specific productivity of the bioconversion has been increased further by amplification of the cytochrome P450 monooxygenase and NADPH-cytochrome reductase genes encoding the rate-limiting omega-hydroxylase in the omega-oxidation pathway. The amplified strains demonstrated increased omega-hydroxylase activity and a 30% increase in productivity compared to the beta-oxidation-blocked strain in fermentations. The bioconversion is effective for the selective terminal oxidation of both saturated and unsaturated linear aliphatic substrates with chain-lengths ranging from 12 carbons to 22 carbons and also avoids the undesirable chain modifications associated with passage through the beta-oxidation pathway, such as unsaturation, hydroxylation, or chain shortening. It is now possible to efficiently produce a wide range of previously unavailable saturated and unsaturated dicarboxylic acids with a high degree of purity.
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PMID:Metabolic engineering of Candida tropicalis for the production of long-chain dicarboxylic acids. 136 84

In the present study on male rainbow trout, well-defined microsomal fractions from gonad, trunk kidney, and head kidney were used to study enzymes active on progesterone. The metabolites produced were identified by mass spectrometric analysis. In the testis the main metabolite was 17 alpha-hydroxyprogesterone which is an intermediate in the steroid biosynthetic pathway. 17 alpha-Hydroxyprogesterone was also identified in incubations from head and trunk kidney. The 17 alpha-hydroxylase activity was higher in the head kidney than in the trunk kidney which probably reflects the presence of steroid producing interrenal cells in this part of the kidney. The conversion of progesterone to 17 alpha-hydroxylated products in the testis and head kidney was NADPH dependent and inhibited by carbon monoxide, indicating the participation of cytochrome P450 monooxygenase in this reaction. NADH supported the reaction to some extent (27% of the NADPH-dependent activity) in the testis but not in the head kidney. In addition to 17 alpha-hydroxyprogesterone the head and trunk kidney microsomes gave rise to 16 alpha- and 6 beta-hydroxyprogesterone. These activities were low or absent in testis microsomes. Progesterone 5 alpha-reductase activity was only detected in trunk kidney microsomes.
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PMID:Progesterone metabolism in the microsomal fraction of the testis, head kidney, and trunk kidney from the rainbow trout. 235 75

To understand better the biochemical genetics of cytochrome P450 monooxygenase-mediated insecticide resistance, we examined the microsomal monooxygenases in insecticide-susceptible (aabys) and pyrethroid-resistant (LPR) house fly strains, as well as 15 house fly lines derived from crosses of LPR and aabys. In comparison to the aabys strain, LPR had higher levels of total cytochromes P450, cytochrome b5, P450 reductase, CYP6D1, and three P450 monooxygenase activities: 7-ethoxycoumarin O-deethylase (ECOD), methoxyresorufin O-demethylase (MROD), and aromatic hydrocarbon hydroxylase (AHH). The elevated levels of cytochrome b5 were linked to factors on autosomes 1 and 2. This is similar to previous reports on monooxygenase-mediated resistance and is consistent with the idea that elevated cytochrome b5 levels are involved in monooxygenase-mediated resistance in the LPR strain. Linkage of the elevated P450 reductase is different from that of monooxygenase-mediated resistance. Strains having high levels of CYP6D1 (i.e., like LPR) had high levels of P450 reductase, while strains having intermediate levels of CYP6D1 also had high levels of reductase. Therefore, there is no clear evidence that the elevated P450 reductase in the LPR strain is required for the increased monooxygenase activity. Overexpression of total cytochromes P450, CYP6D1 (mRNA and protein), and CYP6D1-mediated monooxygenase activities (MROD and AHH) in LPR microsomes was linked to a combination of factors on autosomes 1 and 2. This demonstrates that increased expression of CYP6D1 in the LPR strain is both cis regulated by a factor(s) on autosome 1 and trans regulated by a factor(s) on autosome 2. The correlation between the overexpression of CYP6D1 mRNA and protein suggests that CYP6D1 expression is regulated transcriptionally. Monooxygenase-mediated resistance in LPR is controlled by factors on autosomes 1 and 2, which supports previous claims that CYP6D1 is responsible for monooxygenase-mediated resistance in the LPR strain.
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PMID:Genetic analysis of factors controlling high-level expression of cytochrome P450, CYP6D1, cytochrome b5, P450 reductase, and monooxygenase activities in LPR house flies, Musca domestica. 873 13

The systematic sequencing of anonymous cDNA clones (expressed sequence tags or ESTs) from the plant Arabidopsis thaliana has identified a number of cDNAs with similarity to known cytochrome P450 sequences. The partial sequence of one of these cDNAs, 5G6, indicated that it was likely to encode a full-length cytochrome P450 monooxygenase (cyt P450) sequence. In this paper we describe the complete sequence of this clone, which has been designated CYP71B7 in accordance with the nomenclature for the cyt P450 gene superfamily. The cDNA was used to determine the pattern of expression of the corresponding gene in A. thaliana. Northern hybridization analysis indicated that maximal expression of CYP71B7 occurred in rosette leaves. Weaker hybridizing bands were also detected by Northern analysis of RNA from roots, leaves, flowers, and siliques. No expression could be detected in stem tissue. Southern analysis indicated that the CYP71B7 gene was likely to exist as a single copy in the genome of A. thaliana. CYP71B7 was expressed episomally in yeast, and microsomes prepared from transgenic yeast exhibited a carbon monoxide difference spectrum characteristic of cyt P450. Microsomes from yeast expressing CYP71B7 were assayed for enzymatic activity with synthetic model cyt P450 substrates. Microsomes from yeast cells expressing CYP71B7 or those from control cells exhibited no detectable NADPH-supported 7-ethoxycoumarin or 7-ethoxyresorufin deethylase activities. However, in the presence of cumene hydroperoxide, activity was observed with microsomes from cells expressing CYP71B7 with 7-ethoxycoumarin as substrate. Organic hydroperoxides are well known to support cyt P450 catalysis in the absence of electrons from NADPH. The yeast microsomes contained high levels of endogenous NADPH-ferricytochrome P450 reductase (CPR) activity. The data suggest that this A. thaliana cyt P450, although expressed in an active form, is incapable of accepting electrons from the endogenous yeast CPR protein.
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PMID:Expression of CYP71B7, a cytochrome P450 expressed sequence Tag from Arabidopsis thaliana. 914 59

The cytochrome P450 monooxygenase system consists of NADPH-cytochrome P450 reductase (P450 reductase) and cytochromes P450, which can catalyze the oxidation of a wide variety of endogenous and exogenous compounds. P450 reductase transfers reducing equivalents from NADPH to P450, which in turn catalyzes metabolic reactions. In previous studies, we have used the rat glioma C6 cell line as an in vitro model system and identified the presence of P450 reductase and of cytochrome P450 1A1, 1A2, 2A1, 2B1/2, 2C7, 2D1-5 and 2E1 by reverse transcription followed by polymerase chain reaction (RT-PCR). In C6 cells, the induction of P450 1A1 and 2B1/2 at mRNA level after BA (benzo(a)anthracene) or PB (phenobarbital) treatments was detected. In this study, analysis of microsomal preparations of glioma C6 cells was utilized to demonstrate the presence of P450 2B and P450 reductase at the protein level. ELISAs showed that PB induced P450 2B proteins 12-fold. These experiments further establish that the rat glioma C6 cell line contains an active cytochrome P450 monooxygenase system that can be induced by P450 inducers. We also found that the mRNAs of P450 1A1 and 2B1/2 from glioma C6 cells do not bind to the oligo(dT)-based separation techniques efficiently, suggesting that they may have very short poly(A) tails. The half-lives of P450 1A1 and 2B1/2 mRNA in glioma C6 cells are 1/10 and 1/3 of that in liver, respectively. This may partly contribute to the low expression level of P450s in glial cells. The induction of P450s by BA or PB did not change their mRNA half-lives, indicating the induction may be due to transcriptional regulation. In summary of this study, we believe the presence of the cytochrome P450 monooxygenase system in glial cells of the brain may be important in chemotherapy and carcinogenesis of brain tumors.
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PMID:Expression, induction and regulation of the cytochrome P450 monooxygenase system in the rat glioma C6 cell line. 951 47

Coexpression of cytochrome P450 monooxygenases (CYPs) and reductase was found in human gastric mucosa with intestinal metaplasia. Immunohistochemistry showed reactivity to P450 reductase in metaplastic epithelial cells and in pyloric gland cells in glands showing intestinal metaplasia. These cells exhibit NADPH-diaphorase activity. Reverse transcription-PCR analysis and Western blotting showed that CYP1A1 and CYP1A2 were expressed in specimens with intestinal metaplasia. Tissue distribution of CYP1A1 coincided with that of P450 reductase. However, immunoreactivity to CYP1A2 protein was localized only in the pyloric gland cells near the intestinal metaplastic gland. Salmonella typhimurium mutagen assay definitively revealed that microsomes prepared from gastric mucosa with intestinal metaplasia, in particular in the pyloric gland, functionally activated benzo(a)pyrene and 2-amino-3-methylimidazo [4,5-f]quinoline. These results indicate that carcinogen activation by CYP enzymes expressed in the gastric mucosa may contribute to carcinogenesis of the stomach.
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PMID:Mutagenic activation of environmental carcinogens by microsomes of gastric mucosa with intestinal metaplasia. 1046 77

Prespawning, adult male and female carp, Cyprinus carpio, were intraperitoneally injected with a single dose of 500 microg/kg of 17alpha-ethynylestradiol (EE2). Blood samples were taken and vitellogenin levels were recorded previous to the injection and 8 days afterward. Western blot analysis of plasma VTG showed a marked response in both males (90-fold) and females (67-fold) after EE2 injection. Also, a significant inhibition of the cytochrome P450 monooxygenase system, namely, 7-ethoxyresorufin O-deethylase (EROD) activity, as well as immunodetected CYP1A protein was observed in the EE2-injected fish. Other cytochrome P450 isozymes, such as CYP3A or NADH cyt (b5) reductase, did not indicate any particular trend; whereas NADPH cyt (P450) reductase was significantly induced in EE2-injected animals. Total cytochrome P450, glutathion S-transferase (GST), and total glutathion peroxidase (GPX) fluctuated in a similar manner, but differences among treated and nontreated animals were not statistically significant. UDP glucuronyl transferase (UDPGT), similar to the antioxidant enzymes catalase, superoxide dismutase (SOD), and Se-GPX, progressively decreased in carrier and injected animals in comparison to the controls, although this trend did not reach statistical significance either.
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PMID:Vitellogenin induction and other biochemical responses in carp, Cyprinus carpio, after experimental injection with 17 alpha-ethynylestradiol. 1078 1

Fumonisins are mycotoxins that cause several fatal animal diseases, including cancer in rats and mice. These toxins are produced by several Fusarium species, including the maize pathogen Fusarium verticillioides, and can accumulate in maize infected with the fungus. We have identified four F. verticillioides genes (FUM6, FUM7, FUM8, and FUM9) adjacent to FUM5, a previously identified polyketide synthase gene that is required for fumonisin biosynthesis. Gene disruption analysis revealed that FUM6 and FUM8 are required for fumonisin production and Northern blot analysis revealed that expression of all four recently identified genes is correlated with fumonisin production. Nucleotide sequence analysis indicated that the predicted FUM6 translation product is most similar to cytochrome P450 monooxygenase-P450 reductase fusion proteins and the predicted products of FUM7, FUM8, and FUM9 are most similar to type III alcohol dehydrogenases, class-II alpha-aminotransferases, and dioxygenases, respectively. Together, these data are consistent with FUM5 through FUM9 being part of a fumonisin biosynthetic gene cluster in F. verticillioides.
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PMID:Characterization of four clustered and coregulated genes associated with fumonisin biosynthesis in Fusarium verticillioides. 1172 54

A comparative study has been performed on populations of Unionidae from the Lake Suszek and Brda river situated in the centre of Tucholski Landscape Park, around which there are no factories and the Pilica river--affected by the influence of the nearby town agglomeration. Mussels collected from Suszek were also treated (72 h) with various concentrations of dichlorophenol (DCP; 0.1, 0.15, 0.2 ppm) and paraquat (PQ; 1, 5, 10 ppm) in laboratory conditions (aquarium). The activities of glutathione S-transferase (GST) and cytochrome P450 monooxygenase system (NAD(P)H ferricyanide reductase, NAD(P)H cytochrome c reductase), cytochrome P450 content and b(5) in microsomal and cytosolic fractions of digestive gland were investigated. The differences in enzyme activities between groups of mussels, which were exposed to various concentrations of chemical pollutants, as well as the dependence on geographical distribution in Poland, were observed. In experiments with DCP the dose-dependent increase in GST activity was found, but no changes after PQ treatment were observed. Results, in experiments with DCP and PQ, have varied from no change to increase or decrease in the measured monooxygenase activities and cytochrome P450 content. Increases have been recorded in two cases (NADPH ferricyanide reductase and cytochrome P450) after exposure to DCP and in the case of NADH ferricyanide reductase following the exposure to PQ. NAD(P)H cytochrome c reductase activity and content of P450 decreased considerably in 5 and 10 ppm PQ-treated mussels. Thus, the treatment with DCP and PQ in water changed the properties of the mussels digestive gland cytochrome P450 monooxygenase system. These changes may be used as a bioindicator, at the molecular level, of exposure to those xenobiotics not only in controlled experiments (aquaria) but also in the natural environment.
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PMID:Comparative study of the xenobiotic metabolising system in the digestive gland of the bivalve molluscs in different aquatic ecosystems and in aquaria experiments. 1229 71

Cytochrome b(5), a 17-kDa hemeprotein associated primarily with the endoplasmic reticulum of eukaryotic cells, has long been known to augment some cytochrome P450 monooxygenase reactions, but the mechanism of stimulation has remained controversial. Studies in recent years have clarified this issue by delineating three pathways by which cytochrome b(5) augments P450 reactions: direct electron transfer of both required electrons from NADH-cytochrome b(5) reductase to P450, in a pathway separate and independent of NADPH-cytochrome P450 reductase; transfer of the second electron to oxyferrous P450 from either cytochrome b(5) reductase or cytochrome P450 reductase; and allosteric stimulation of P450 without electron transfer. Evidence now indicates that each of these pathways is likely to operate in vivo.
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PMID:The roles of cytochrome b5 in cytochrome P450 reactions. 1248 6


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