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cytochrome P450 reductase

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https://www.readbyqxmd.com/read/29778238/interplay-between-estrogen-related-receptors-and-steroidogenesis-controlling-molecules-in-adrenals-in-vivo-and-in-vitro-study
#1
A Pacwa, E Gorowska-Wojtowicz, A Ptak, P Pawlicki, A Milon, M Sekula, K Lesniak, B Bilinska, A Hejmej, M Kotula-Balak
Estrogen-related receptors (ERRs) α, β and γ appear to be novel molecules implicated in estrogen signaling. We blocked and activated ERRs in mouse (C57BL/6) adrenals and adrenocortical cells (H295R) using pharmacological agents XCT 790 (ERRα antagonist) and DY131 (ERRβ/γ agonist), respectively. Mice were injected with XCT 790 or DY131 (5 μg/kg bw) while cells were exposed to XCT 790 or DY131 (0.5 μg/L). Irrespectively of the agent used, changes in adrenocortical cell morphology along with changes in lutropin, cholesterol levels and estrogen production were found...
May 16, 2018: Acta Histochemica
https://www.readbyqxmd.com/read/29772534/trapping-methods-for-probing-functional-intermediates-in-nitric-oxide-synthases-and-related-enzymes
#2
Tobias Michael Hedison, Sam Hay, Nigel Shaun Scrutton
The three mammalian isoforms of nitric oxide synthase (NOS) produce the signalling molecule nitric oxide (NO) from L-arginine, molecular oxygen, and NADPH. NOS-generated NO is essential for many key biochemical processes and aberrant NO production is linked to the pathophysiology of many diseases. Over the past 40 years, the mechanism and structure of NOS have been studied extensively and there are many quality reviews and perspectives documenting the current hypotheses in the field. In this review, as an alternative perspective, we will describe some novel techniques and methodologies that have been used to trap functionally relevant conformational and kinetic states in the catalytic cycles of NOS and some structurally related diflavin oxidoreductase...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29755560/anti-hypercholesterolemic-effect-of-berbamine-isolated-from-rhizoma-coptidis-in-hypercholesterolemic-zebrafish-induced-by-high-cholesterol-diet
#3
Bing Han, Shuming Kou, Kai He, Yulong Han, Yue Wang, Tao Huang, Xia Zhou, Yubo Xiao, Xuegang Li, Xiaoli Ye
The anti-hypercholesterolemic effect of berbamine (BBM) isolated from Rhizoma Coptidis (RC) was investigated in hypercholesterolemic zebrafish model induced by high-cholesterol (HC) diet. Zebrafish embryo assay revealed no significant difference in morphology and cell death with the treatment of BBM less than 20 μg/mL. In zebrafish larvae, the fluorescently labeled cholesterol in caudal artery was reduced dose-dependently after BBM treatment. For adult zebrafish, administration of 0.2% BBM exhibited a significant decrease in plasma total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-c) levels by 37%, 38% and 28%, respectively, along with a fall in lipid content in liver...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29754445/engineering-the-unicellular-alga-phaeodactylum-tricornutum-for-high-value-plant-triterpenoid-production
#4
Sarah D'Adamo, Gino Schiano di Visconte, Gavin Lowe, Joanna Szaub-Newton, Tracey Beacham, Andrew Landels, Michael J Allen, Andrew Spicer, Michiel Matthijs
Plant triterpenoids constitute a diverse class of organic compounds that play a major role in development, plant defense and environmental interaction. Several triterpenes have demonstrated potential as pharmaceuticals. One example is betulin, which has shown promise as a pharmaceutical precursor for the treatment of certain cancers and HIV. Major challenges for triterpenoid commercialization include their low production levels and their cost-effective purification from the complex mixtures present in their natural hosts...
May 13, 2018: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/29726954/heterologous-co-expression-of-cyp6b7-and-nadph-dependent-cytochrome-p450-reductase-from-helicoverpa-armigera-lepidoptera-noctuidae-in-pichia-pastoris
#5
Chunqing Zhao, Genmiao Song, Kristopher Silver, Tao Tang, Chen Wang, Lihong Qiu
As important metabolic enzymes, the function of cytochrome P450 monooxygenases (CYPs) has been demonstrated repeatedly through various means, including heterologous expression systems. Unfortunately, most model systems typically lack expression of a conspecific NADPH-dependent cytochrome P450 reductase (CPR), which is the electron transfer partner of CYPs. As a result, the activities of heterologously expressed insect CYPs may not accurately reflect detoxification activities in vivo. Previously, CYP6B7 from Helicoverpa armigera (Hübner) (Lepidoptera: Noctuidae) (HaCYP6B7) has been expressed in the Pichia pastoris GS115 strain and shown to detoxify bifenthrin, fenvalerate and chlorpyrifos...
May 3, 2018: Journal of Economic Entomology
https://www.readbyqxmd.com/read/29722926/a-minimal-functional-complex-of-cytochrome-p450-and-fbd-of-cytochrome-p450-reductase-in-nanodiscs
#6
Elke Prade, Mukesh Mahajan, Sang-Choul Im, Meng Zhang, G M Anantharamaiah, Lucy Waskell, Ayyalusamy Ramamoorthy
Structural interactions that enable electron transfer to cytochrome-P450 (CYP450) from its redox partner CYP450-reductase (CPR) are a vital prerequisite for its catalytic mechanism. Here, we report the first structural model for the membrane-bound functional complex to reveal interactions between the full-length CYP450 and a minimal domain of CPR. Our results suggest that anchorage of the proteins in a lipid bilayer is a minimal requirement for CYP450 catalytic function. Akin to cytochrome-b5 (cyt-b5), Arg125 on the C-helix of CYP450s is found to be important for effective electron transfer, thus supporting the competitive behavior of redox partners for CYP450s...
May 3, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29684698/biophysical-characterization-of-aptenodytes-forsteri-cytochrome-p450-aromatase
#7
Francisco Zarate-Perez, Jesús B Velázquez-Fernández, Gareth K Jennings, Lisa S Shock, Charles E Lyons, John C Hackett
Cytochrome P450 19 (CYP19, aromatase) catalyzes the conversion of androgens to estrogens in a sequence of three reactions that each depend on NADPH and O2 . Aromatase is a phylogenetically-ancient enzyme and its breadth of expression in other species has highlighted distinct physiological functions. In songbirds, estrogen production is required for programming the neural circuits controlling song and in the determination of sex in fish and reptiles. This work describes the expression, purification, and biophysical characterization of Aptenodytes forsteri (Emperor penguin, af) aromatase...
April 7, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29679043/identification-and-heterologous-expression-of-the-actinoallolide-biosynthetic-gene-cluster
#8
Yuki Inahashi, Taro Shiraishi, Akira Také, Atsuko Matsumoto, Yōko Takahashi, Satoshi Ōmura, Tomohisa Kuzuyama, Takuji Nakashima
Actinoallolides are anti-trypanosomal macrolides isolated from the secondary metabolites of two endophytic actinomycete strains, Actinoallomurus fulvus MK10-036 and K09-0307. A putative actinoallolide biosynthetic gene cluster was predicted from the genome sequence of the strain K09-0307. The gene cluster spans a contiguous 53 kb DNA region that comprises seven genes encoding three PKSs (aalA1, aalA2, and aalA3), cytochrome P450 (aalB), acyl-CoA dehydrogenase (aalC), crotonyl-CoA reductase (aalD), and TetR family regulator (aalR)...
April 20, 2018: Journal of Antibiotics
https://www.readbyqxmd.com/read/29674492/11beta-hydroxysteroid-dehydrogenase-1-human-tissue-distribution-selective-inhibitor-and-role-in-doxorubicin-metabolism
#9
Xin Yang, Wenyi Hua, Sangwoo Ryu, Phillip Yates, Cheng Chang, Hui Zhang, Li Di
11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) is mainly distributed in the human liver with no detectable levels in the intestine or kidney based on a newly developed proteomic approach. 11β-HSD1 is mostly membrane bound and retained in the liver microsomal faction. Inter-individual variability of 11β-HSD1 is relatively low with about a three-fold difference. A significant correlation was not observed between various demographic variables (ethnicity, gender, age, weight, smoking, and alcohol use) and 11β-HSD1 protein expression or activity based on data from thirty-one donors...
April 19, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29668912/ovine-placental-steroid-synthesis-and-metabolism-in-late-gestation
#10
Lawrence P Reynolds, Erin L Legacki, C Jo Corbin, Joel S Caton, Kimberly A Vonnahme, Scott Stanley, Alan J Conley
Steroid synthesis is required for pregnancy maintenance and for parturition but comparatively little is known about the major metabolic routes that influence circulating concentrations. Dietary intake changes progesterone and estradiol concentrations in pregnant ewes but whether this reflects placental synthesis is unknown. Progesterone metabolism by 5alpha-reduction is a major metabolic route in other species and can influence the onset of parturition. Therefore, studies were conducted to 1) determine placental enzyme activity, progesterone and estradiol measured by immuno-assay in late gestation ewes on low, moderate and high nutritional planes, 2) to assess the significance of 5alpha-reduction of progesterone in determining progesterone concentrations in late gestation ewes (gestation day 145) given finasteride to inhibit 5alpha-reductase metabolism...
April 14, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29663675/a-stable-artificial-multienzymatic-complex-using-a-heterotrimeric-protein-from-metallosphaera-sedula
#11
Fumiya Iwata, Hidehiko Hirakawa, Teruyuki Nagamune
Bacterial cytochrome P450 monooxygenases (P450s) are promising biocatalysts for chemical syntheses because they catalyze a variety of oxidations on non-activated hydrocarbons using O2 . However, the requirement of two auxiliary proteins, an electron transfer protein and a reductase, for the catalysis is a major bottleneck for in vitro applications of these monooxygenases. Our previous study showed that artificial assembly of a bacterial P450 with its auxiliary proteins using a heterotrimeric proliferating cell nuclear antigen (PCNA) from Sulfolobus solfataricus yields a self-sufficient P450, but partial dissociation of P450 from the complex at catalytic concentrations reduces the apparent specific activity of this self-sufficient P450...
April 16, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29656332/rdh13-deficiency-weakens-carbon-tetrachloride-induced-liver-injury-by-regulating-spot14-and-cyp2e1-expression-levels
#12
Xiaofang Cui, Benting Ma, Yan Wang, Yan Chen, Chunling Shen, Ying Kuang, Jian Fei, Lungen Lu, Zhugang Wang
Mitochondrion-localized retinol dehydrogenase 13 (Rdh13) is a short-chain dehydrogenase/reductase involved in vitamin A metabolism in both humans and mice. We previously generated Rdh13 knockout mice and showed that Rdh13 deficiency causes severe acute retinal light damage. In this study, considering that Rdh13 is highly expressed in mouse liver, we further evaluated the potential effect of Rdh13 on liver injury induced by carbon tetrachloride (CCl4 ). Although Rdh13 deficiency showed no significant effect on liver histology and physiological functions under regular culture, the Rdh13-/- mice displayed an attenuated response to CCl4 -induced liver injury...
April 14, 2018: Frontiers of Medicine
https://www.readbyqxmd.com/read/29618513/the-full-length-cytochrome-p450-enzyme-cyp102a1-dimerizes-at-its-reductase-domains-and-has-flexible-heme-domains-for-efficient-catalysis
#13
Haoming Zhang, Adam L Yokom, Shen Cheng, Min Su, Paul F Hollenberg, Daniel R Southworth, Yoichi Osawa
The cytochrome P450 enzyme CYP102A1 from Bacillus megaterium is a highly efficient hydroxylase of fatty acids, and there is a significant interest in using CYP102A1 for biotechnological applications. Here we used size-exclusion chromatography-multiangle light scattering (SEC-MALS) analysis and negative-stain EM to investigate the molecular architecture of CYP102A1. The SEC-MALS analysis yielded a homogeneous peak with an average molecular weight of 235 ± 5 kDa, consistent with homodimeric CYP102A1. The negative-stain EM of dimeric CYP102A1 revealed four distinct lobes, representing the two heme and two reductase domains...
April 4, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29603629/cyp3a5-3-and-abcb1-61a-g-significantly-influence-dose-adjusted-trough-blood-tacrolimus-concentrations-in-the-first-three-months-post-kidney-transplantation
#14
Rong Hu, Daniel T Barratt, Janet K Coller, Benedetta C Sallustio, Andrew A Somogyi
Tacrolimus (TAC) is a first-line immunosuppressant used to prevent organ rejection after kidney transplantation. There is large inter-individual variability in its pharmacokinetics. Single nucleotide polymorphisms (SNPs) in genes encoding TAC metabolising enzymes cytochromes P450 3A4/5 (CYP3A4/5), P-glycoprotein efflux transporter (ABCB1), their expression regulator pregnane X receptor (NR1I2), and CYP3A co-factor cytochrome P450 reductase (POR), have been studied for their effects on tacrolimus disposition...
March 30, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29602381/cloning-expression-and-characterisation-of-p450-hal1-cyp116b62-from-halomonas-sp-ncimb-172-a-self-sufficient-p450-with-high-expression-and-diverse-substrate-scope
#15
Joanne L Porter, Selina Sabatini, Jack Manning, Michele Tavanti, James L Galman, Nicholas J Turner, Sabine L Flitsch
Cytochrome P450 monooxygenases are able to catalyse a range of synthetically challenging reactions ranging from hydroxylation and demethylation to sulfoxidation and epoxidation. As such they have great potential for biocatalytic applications but are underutilised due to often-poor expression, stability and solubility in recombinant bacterial hosts. The use of self-sufficient P450 s with fused haem and reductase domains has already contributed heavily to improving catalytic efficiency and simplifying an otherwise more complex multi-component system of P450 and redox partners...
June 2018: Enzyme and Microbial Technology
https://www.readbyqxmd.com/read/29589597/correction-the-hinge-segment-of-human-nadph-cytochrome-p450-reductase-in-conformational-switching-the-critical-role-of-ionic-strength
#16
Diana Campelo, Thomas Lautier, Philippe Urban, Francisco Esteves, Sophie Bozonnet, Gilles Truan, Michel Kranendonk
[This corrects the article on p. 755 in vol. 8, PMID: 29163152.].
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29584635/the-synthesis-of-molecular-docking-studies-in-vitro-antimicrobial-and-antifungal-activities-of-novel-dipeptide-derivatives-based-on-n-2-2-hydrazinyl-2-oxoethylamino-2-oxoethyl-nicotinamide
#17
Gaber Moustafa, Hemat Khalaf, Ahmed Naglah, Asma Al-Wasidi, Nawal Al-Jafshar, Hassan Awad
A series of linear dipeptide derivatives ( 4 - 10 ) were prepared and evaluated as antimicrobial agents via the synthesis of N -(2-(2-hydrazinyl-2-oxoethylamino)-2-oxoethyl) nicotinamide ( 4 ). Compound 4 was reacted with 4-chlorobenzaldehyde or 4-hydroxybenzaldehyde, to give the hydrazones 5 and 6 , respectively. On the other hand, Compound 4 was coupled with phenylisocyanate or methylisothiocyanate to give Compounds 7 and 8 , respectively. The latter compounds ( 7 and 8 ) were coupled with chloroacetic acid to give oxazolidine ( 9 ) and thiazolidine ( 10 ), respectively...
March 27, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29577257/pharmacogenetics-of-vitamin-k-antagonists-and-bleeding-risk-prediction-in-atrial-fibrillation
#18
María José Serna, José Miguel Rivera-Caravaca, Rocío Gonzalez-Conejero, María Asunción Esteve-Pastor, Mariano Valdés, Vicente Vicente, Gregory Y H Lip, Vanessa Roldán, Francisco Marín
BACKGROUND: Polymorphisms in the vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genes increase the bleeding risk in anticoagulated atrial fibrillation (AF) patients. Here, we aimed to investigate whether VKORC1 and CYP2C9 polymorphisms improved the predictive performance for major bleeding using the HAS-BLED score. MATERIAL AND METHODS: We recruited 652 consecutive AF patients stable on vitamin K antagonist (INR 2.0-3.0) during at least the previous 6 months...
March 25, 2018: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29568933/effects-and-mechanism-of-amyloid-%C3%AE-1-42-on-mitochondria-in-astrocytes
#19
Yunyi Yao, Jin-Zhong Huang, Yingqi Chen, He-Juan Hu, Xiying Tang, Xianhong Li
Amyloid β (Aβ)1-42 is strongly associated with Alzheimer's disease (AD). The effects of Aβ1‑42 on astrocytes remain largely unknown. The present study focused on the effects of Aβ1‑42 on U87 human glioblastoma cells as astrocytes for in vitro investigation and mouse brains for in vivo investigation. The mechanism and regulation of mitochondria and cytochrome P450 reductase (CPR) were also investigated. As determined by MTT assays, low doses of Aβ1‑42 (<1 µM) marginally promoted astrocytosis compared with the 0 µM group within 24 h, however, after 48 h treatment these doses reduced cellular growth compared with the 0 µM group...
May 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29552849/-cloning-and-functional-identification-of-a-new-nadph-cytochrome-p450-reductase-in-andrographis-paniculata
#20
Meng-Die Qi, Jian Wang, Xiao-Jing Ma, Quan Zhang, Fang-Fang Wang, Ying Kang, Hui-Xin Lin, Yong Liu
Andrographolide is a main active ingredient in traditional Chinese medicine Andrographis paniculata,with a variety of pharmacological activity,widely used in clinical practice. However its biosynthetic pathway has not been resolved. Cytochrome P450 reductase provides electrons for CYP450 and plays an important role in the CYP450 catalytic process. In this study,the coding sequence of A. paniculata CPR was screened and cloned by homologous alignment,named ApCPR4. The ApCPR4 protein was obtained by prokaryotic expression...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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