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cytochrome P450 reductase

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https://www.readbyqxmd.com/read/29148818/dissociation-constants-of-cytochrome-p450-2c9-cytochrome-p450-reductase-complexes-in-a-lipid-bilayer-membrane-depend-on-nadph-a-single-protein-tracking-study
#1
Carlo Barnaba, Evan Taylor, James A Brozik
Cytochrome P450-Reductase (CPR) is a versatile NADPH-dependent electron donor located in the cytoplasmic side of the endoplasmic reticulum. It is an electron transferase that is able to deliver electrons to a variety of membrane-bound oxidative partners, including the drug-metabolizing enzymes of the cytochrome P450s (P450). CPR is also stoichiometrically limited compared to its oxidative counterparts and hypotheses have arisen about possible models that can overcome the stochiometric imbalance, including quaternary organization of P450 and diffusion-limited models...
November 17, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29104319/cytochrome-b5-plays-a-dual-role-in-the-reaction-cycle-of-cytochrome-p450-3a4-during-oxidation-of-the-anticancer-drug-ellipticine
#2
Marie Stiborová, Radek Indra, Eva Frei, Kateřina Kopečková, Heinz H Schmeiser, Tomáš Eckschlager, Vojtěch Adam, Zbyněk Heger, Volker M Arlt, Václav Martínek
Abstract: Ellipticine is an anticancer agent that forms covalent DNA adducts after enzymatic activation by cytochrome P450 (CYP) enzymes, mainly by CYP3A4. This process is one of the most important ellipticine DNA-damaging mechanisms for its antitumor action. Here, we investigated the efficiencies of human hepatic microsomes and human recombinant CYP3A4 expressed with its reductase, NADPH:CYP oxidoreductase (POR), NADH:cytochrome b5 reductase and/or cytochrome b5 in Supersomes™ to oxidize this drug...
2017: Monatshefte Für Chemie
https://www.readbyqxmd.com/read/29104317/comparison-of-human-cytochrome-p450-1a1-catalysed-oxidation-of-benzo-a-pyrene-in-prokaryotic-and-eukaryotic-expression-systems
#3
Marie Stiborová, Radek Indra, Michaela Moserová, Lucie Bořek-Dohalská, Petr Hodek, Eva Frei, Klaus Kopka, Heinz H Schmeiser, Volker M Arlt
Abstract: Cytochrome P450 (CYP) 1A1 is the most important enzyme activating and detoxifying the human carcinogen benzo[a]pyrene (BaP). In the previous studies, we had shown that not only the canonic NADPH:CYP oxidoreductase (POR) can act as electron donor but also cytochrome b5 and its reductase, NADH:cytochrome b5 reductase. Here, we studied the role of the expression system used on the metabolites generated and the levels of DNA adducts formed by activated BaP. We used an eukaryotic and a prokaryotic cellular system (Supersomes, microsomes isolated from insect cells, and Bactosomes, a membrane fraction of Escherichia coli, each transfected with cDNA of human CYP1A1 and POR)...
2017: Monatshefte Für Chemie
https://www.readbyqxmd.com/read/29098926/the-impact-of-sesquiterpenes-%C3%AE-caryophyllene-oxide-and-transnerolidol-on-xenobiotic-metabolizing-enzymes-in-mice-in-vivo
#4
Kateřina Lněničková, Hana Svobodová, Lenka Skálová, Martin Ambrož, Filip Novák, Petra Matoušková
1. Sesquiterpenes, constituents of plant essential oil, are popular bioactive compounds due to the positive effect on human health, but their potential toxicity and possible herb-drug interactions are often omitted. In our in vivo study, we followed up the effect of p.o. administration of two sesquiterpenes β-caryophyllene oxide (CAO) and trans-nerolidol (NER) on various xenobiotic-metabolizing enzymes in mice liver and small intestine. 2. To spot the early effect of studied compounds, enzymatic activity and mRNA levels were assessed 6 and 24 h after single dose...
November 3, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29096092/enzymatic-activity-and-gene-expression-changes-in-zebrafish-embryos-and-larvae-exposed-to-pesticides-diazinon-and-diuron
#5
Mirna Velki, Henriette Meyer-Alert, Thomas-Benjamin Seiler, Henner Hollert
The zebrafish as a test organism enables the investigation of effects on a wide range of biological levels from molecular level to the whole-organism level. The use of fish embryos represents an attractive model for studies aimed at understanding toxic mechanisms and the environmental risk assessment of chemicals. In the present study, a zebrafish (Danio rerio) in vivo model was employed in order to assess the effects of two commonly used pesticides, the insecticide diazinon and the herbicide diuron, on zebrafish early life stages...
October 28, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29081786/probing-the-single-key-amino-acid-responsible-for-the-novel-catalytic-function-of-ent-kaurene-oxidase-supported-by-nadph-cytochrome-p450-reductases-in-tripterygium-wilfordii
#6
Ping Su, Hongyu Guan, Yifeng Zhang, Xing Wang, Linhui Gao, Yujun Zhao, Tianyuan Hu, Jiawei Zhou, Baowei Ma, Lichan Tu, Yuru Tong, Luqi Huang, Wei Gao
Tripterygium wilfordii produces not only ent-kaurene, which is an intermediate of gibberellin (GA) biosynthesis in flowering plants, but also 16α-hydroxy-ent-kaurane, whose physiological role has not been characterized. The two compounds are biosynthesized from the universal diterpenoid precursor (E,E,E)-geranylgeranyl diphosphate (GGPP) by diterpene synthases, which have been discovered and functionally characterized in T. wilfordii. Here, we described the functional characterization of four cytochrome P450 reductases (TwCPR) and one ent-kaurene oxidase (TwKO)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29079474/design-synthesis-and-biological-evaluation-of-pyrrolobenzodiazepine-containing-hypoxia-activated-prodrugs
#7
Peter S Dragovich, Fabio Broccatelli, Jinhua Chen, Peter Fan, Hoa Le, Weiguang Mao, Thomas H Pillow, Andrew G Polson, John Wai, Zijin Xu, Hui Yao, Donglu Zhang
The ability of various pyrrolobenzodiazepine(PBD)-containing cytotoxic compounds to function as hypoxia-activated prodrugs was assessed. These molecules incorporated a 1-methyl-2-nitro-1H-imidazole hypoxia-activated trigger (present in the clinically evaluated compound TH-302) in a manner that masked a reactive imine moiety required for cytotoxic activity. Incubation of the prodrugs with cytochrome P450-reductase under normoxic and hypoxic conditions revealed that some, but not all, were efficient substrates for the enzyme...
October 13, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29072765/the-cytochrome-b5-cybe-is-regulated-by-iron-availability-and-is-crucial-for-azole-resistance-in-a-fumigatus
#8
Matthias Misslinger, Fabio Gsaller, Peter Hortschansky, Christoph Müller, Franz Bracher, Michael J Bromley, Hubertus Haas
Cytochrome P450 enzymes (P450) play essential roles in redox metabolism in all domains of life including detoxification reactions and sterol biosynthesis. The activity of P450s is fuelled by two electron-transferring mechanisms, heme-independent P450 reductase (CPR) and the heme-dependent cytochrome b5 (CYB5)/cytochrome b5 reductase (CB5R) system. In this study, we characterised the role and regulation of the cytochrome b5 CybE in the fungal pathogen Aspergillus fumigatus. Deletion of the CybE encoding gene (cybE) caused a severe growth defect in two different A...
November 15, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/29066529/steroidogenic-enzyme-activities-in-the-pre-and-post-parturient-equine-placenta
#9
Erin Lea Legacki, Cynthia Jo Corbin, Barry A Ball, Kirsten Scoggin, Scott D Stanley, Alan Conley
Steroidogenic enzymes in placentas shape steroid hormone profiles in the maternal circulation of each mammalian species. These include 3β-hydroxysteroid dehydrogenase/Δ5-4 isomerase (3βHSD) and 17α-hydroxylase/17,20-lyase cytochrome P450 (P450c17) crucial for progesterone and androgen synthesis, respectively, as well as aromatase cytochrome P450 (P450arom) that converts Δ4-androgens to estrogens. 5α-reductase is another important enzyme in equine placentas because 5α-dihydroprogesterone (DHP) sustains pregnancy in the absence of progesterone in the second half of equine pregnancy...
October 24, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29064631/ferric-citrate-supplementation-reduces-red-blood-cell-aggregation-and-improves-cd163-macrophage-mediated-hemoglobin-metabolism-in-a-rat-model-of-high-fat-diet-induced-obesity
#10
Ting-Yun Chang, Kai-Li Liu, Cheng Sheng Chang, Chien-Tien Su, Seu-Hwa Chen, Yu-Chieh Lee, Jung-Su Chang
SCOPE: In adults, >90% of the daily iron requirement is derived from macrophage-mediated heme iron recycling from senescent red blood cells (RBCs) or free hemoglobin (Hb). Currently, the effects of pharmacological doses of iron supplementation on RBCs and heme iron recycling in obesity are unclear. METHODS AND RESULTS: Sprague Dawley rats were fed a standard diet or a 50% high-fat diet (HFD) with (0.25, 1, and 2 g of ferric iron/kg diet) or without ferric citrate supplementation for 12 weeks...
October 24, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29040572/biallelic-mutations-in-the-ferredoxin-reductase-gene-cause-novel-mitochondriopathy-with-optic-atrophy
#11
Yanyan Peng, Deepali N Shinde, Alex C Valencia, Jun-Song Mo, Jill Rosenfeld, Megan Truitt Cho, Adam Chamberlin, Zhuo Li, Jie Liu, Baoheng Gui, Rachel Brockhage, Alice Basinger, Brenda Alvarez-Leon, Peter Heydemann, Pilar L Magoulas, Andrea M Lewis, Fernando Scaglia, Solange Gril, Shuk Ching Chong, Matthew Bower, Kristin G Monaghan, Rebecca Willaert, Maria-Renee Plona, Rich Dineen, Francisca Milan, George Hoganson, Zoe Powis, Katherine L Helbig, Jennifer Keller-Ramey, Belinda Harris, Laura C Anderson, Torrian Green, Stacey J Sukoff Rizzo, Julie Kaylor, Jiani Chen, Min-Xin Guan, Elizabeth Sellars, Steven P Sparagana, James B Gibson, Laura G Reinholdt, Sha Tang, Taosheng Huang
Iron-sulfur (Fe-S) clusters are ubiquitous cofactors essential to various cellular processes, including mitochondrial respiration, DNA repair, and iron homeostasis. A steadily increasing number of disorders are being associated with disrupted biogenesis of Fe-S clusters. Here, we conducted whole-exome sequencing of patients with optic atrophy and other neurological signs of mitochondriopathy and identified 17 individuals from 13 unrelated families with recessive mutations in FDXR, encoding the mitochondrial membrane-associated flavoprotein ferrodoxin reductase required for electron transport from NADPH to cytochrome P450...
October 5, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29031061/crassiflorone-derivatives-that-inhibit-trypanosoma-brucei-glyceraldehyde-3-phosphate-dehydrogenase-tbgapdh-and-trypanosoma-cruzi-trypanothione-reductase-tctr-and-display-trypanocidal-activity
#12
Elisa Uliassi, Giulia Fiorani, R Luise Krauth-Siegel, Christian Bergamini, Romana Fato, Giulia Bianchini, J Carlos Menéndez, Maria Teresa Molina, Eulogio López-Montero, Federico Falchi, Andrea Cavalli, Sheraz Gul, Maria Kuzikov, Bernhard Ellinger, Gesa Witt, Carolina B Moraes, Lucio H Freitas-Junior, Chiara Borsari, Maria Paola Costi, Maria Laura Bolognesi
Crassiflorone is a natural product with anti-mycobacterial and anti-gonorrhoeal properties, isolated from the stem bark of the African ebony tree Diospyros crassiflora. We noticed that its pentacyclic core possesses structural resemblance to the quinone-coumarin hybrid 3, which we reported to exhibit a dual-targeted inhibitory profile towards Trypanosoma brucei glyceraldehyde-3-phosphate dehydrogenase (TbGAPDH) and Trypanosoma cruzi trypanothione reductase (TcTR). Following this basic idea, we synthesized a small library of crassiflorone derivatives 15-23 and investigated their potential as anti-trypanosomatid agents...
December 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29030652/evidence-for-a-complex-formation-between-cyp2j5-and-meh-in-living-cells-by-fret-analysis-of-membrane-protein-interaction-in-the-endoplasmic-reticulum-fampir
#13
Anette Carolina Orjuela Leon, Anne Marwosky, Michael Arand
The potential complex formation between microsomal epoxide hydrolase (mEH) and cytochrome P450-dependent monooxygenase (CYP) has been a subject of research for many decades. Such an association would enable efficient substrate channeling between CYP and mEH and as such represent an attractive strategy to prevent deleterious accumulation of harmful metabolic by-products such as CYP-generated epoxide intermediates. However, such complex formation is experimentally difficult to prove, because CYP and mEH are membrane-bound proteins that are prone to unspecific aggregation after solubilization...
October 13, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28992544/the-influence-of-different-light-quality-and-benzene-on-gene-expression-and-benzene-degradation-of-chlorophytum-comosum
#14
Arnon Setsungnern, Chairat Treesubsuntorn, Paitip Thiravetyan
Benzene, a carcinogenic compound, has been reported as a major indoor air pollutant. Chlorophytum comosum (C. comosum) was reported to be the highest efficient benzene removal plant among other screened plants. Our previous studies found that plants under light conditions could remove gaseous benzene higher than under dark conditions. Therefore, C. comosum exposure to airborne benzene was studied under different light quality at the same light intensity. C. comosum could remove 500 ppm gaseous benzene with the highest efficiency of 68...
September 28, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28989052/in-silico-analysis-of-cytochrome-p450-monooxygenases-in-chronic-granulomatous-infectious-fungus-sporothrix-schenckii-special-focus-on-cyp51
#15
Retshedisitswe Godfrey Matowane, Lukasz Wieteska, Hans Denis Bamal, Ipeleng Kopano Rosinah Kgosiemang, Mari Van Wyk, Nessie Agnes Manume, Sara Mohamed Hasaan Abdalla, Samson Sitheni Mashele, Dominik Gront, Khajamohiddin Syed
Sporotrichosis is an emerging chronic, granulomatous, subcutaneous, mycotic infection caused by Sporothrix species. Sporotrichosis is treated with the azole drug itraconazole as ketoconazole is ineffective. It is a well-known fact that azole drugs act by inhibiting cytochrome P450 monooxygenases (P450s), heme-thiolate proteins. To date, nothing is known about P450s in Sporothrix schenckii and the molecular basis of its resistance to ketoconazole. Here we present genome-wide identification, annotation, phylogenetic analysis and comprehensive P450 family-level comparative analysis of S...
October 5, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28982933/steroidogenesis-during-postnatal-testicular-development-of-galea-spixii
#16
P R S Santos, F D Oliveira, M A M Arroyo, M F Oliveira, P Castelucci, A J Conley, A C Assis Neto
The androgen/estrogen balance is essential for normal sexual development and reproduction in mammals. Studies performed herein investigated the potential for estrogen synthesis in cells of the testes of a hystricomorph rodent, Galea spixii The study characterized the expression of the key enzymes responsible for estrogen and androgen synthesis, cytochromes P450 aromatase (P450arom), 17α-hydroxylase/17,20-lyase (P450c17) respectively, as well as the redox partner NADPH cytochrome P450 oxido-reductase (CPR) required to support electron transfer and catalysis of these P450s, by immunohistochemistry (IHC) and quantitative polymerase chain reaction (qPCR) analysis, throughout postnatal sexual development...
November 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28978042/translocation-of-heme-oxygenase-1-contributes-to-imatinib-resistance-in-chronic-myelogenous-leukemia
#17
Bianca Schaefer, Soenke Behrends
Heme oxygenase-1 (HO-1) degrades heme to bilirubin. In addition, it is upregulated in malignant disease and has been described as an important factor for cancer prognosis and therapy. Under physiological conditions HO-1 is anchored to the endoplasmic reticulum (ER). Under stress conditions HO-1 can be cleaved and subsequently translocates to the cytosol and nucleus. In this study we systematically investigated the influence of HO-1's catabolic activity and subcellular localization on resistance against the tyrosine kinase inhibitor imatinib in leukemia cells by confocal laser scanning microscopy, hemoglobin synthesis experiments and cell viability assays...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28976137/effect-of-lupeol-on-antioxidants-and-xenobiotic-enzymes-in-n-butyl-n-4-hydroxybutyl-nitrosamine-induced-bladder-carcinogenesis-in-experimental-rats
#18
Bhoopathy Prabhu, Annamalai Sivakumar, Doraisami Balakrishnan, Sivapatham Sundaresan
Urothelial carcinoma of the bladder is a common malignancy ranked 9(th) with an estimated 356,600 new cases diagnosed annually worldwide. The study showed the protective effects of Lupeol in N-Butyl-N-(4-hydroxybutyl) nitrosamine induced bladder carcinogenesis in in vivo experimental model. Forty male healthy wistar rats were selected randomly divided into four groups. Group I rats served as healthy control. Group II rats were treated with BBN (150 mg/gavage/twice a week) for 8 weeks. Group III rats were treated with BBN + Lupeol [ Lupeol (50 mg/kg bw/day) treatment was started 1 week prior to the BBN treatment, and it was orally administered for 8 weeks]...
September 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/28960749/detoxification-of-ivermectin-by-atp-binding-cassette-transporter-c4-and-cytochrome-p450-monooxygenase-6cj1-in-the-human-body-louse-pediculus-humanus-humanus
#19
J H Kim, K J Gellatly, B Lueke, M Kohler, R Nauen, E Murenzi, K S Yoon, J M Clark
We previously observed that ivermectin-induced detoxification genes, including ATP binding cassette transporter C4 (PhABCC4) and cytochrome P450 6CJ1 (CYP6CJ1) were identified from body lice following a brief exposure to a sublethal dose of ivermectin using a non-invasive induction assay. In this current study, the functional properties of PhABCC4 and CYP6CJ1 were investigated after expression in either X. laevis oocytes or using a baculovirus expression system, respectively. Efflux of [(3) H]-9-(2-phosphonomethoxyethyl) adenine ([(3) H]-PMEA), a known ABCC4 substrate in humans, was detected from PhABCC4 cRNA-injected oocytes by liquid scintillation spectrophotometric analysis and PhABCC4 expression in oocytes was confirmed using ABC transporter inhibitors...
September 27, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/28944003/partial-fusion-of-a-cytochrome-p450-system-by-carboxy-terminal-attachment-of-putidaredoxin-reductase-to-p450cam-cyp101a1
#20
Eachan O Johnson, Luet-Lok Wong
Cytochrome P450 (CYP) enzymes catalyze the insertion of oxygen into carbon-hydrogen bonds and have great potential for enzymatic synthesis. Application development of class I CYPs is hampered by their dependence on two redox partners (a ferredoxin and ferredoxin reductase), slowing catalysis compared to self-sufficient CYPs such as CYP102A1 (P450BM3). Previous attempts to address this have fused all three components in several permutations and geometries, with much reduced activity compared to the native system...
October 21, 2016: Catalysis Science & Technology
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