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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/29778033/weight-and-the-vitamin-k-expoxide-reductase-1-genotype-primarily-contribute-to-the-warfarin-dosing-in-pediatric-patients-with-kawasaki-disease
#2
Zhouping Wang, Li Zhang, Ping Huang, Xiaoqiong Gu, Xiaofei Xie, Yanfei Wang, Wei Li, Qiyi Zeng
INTRODUCTION: Warfarin therapy is recommended in children with giant coronary artery aneurysms (GCAAs) after Kawasaki disease (KD). Large individual variability makes it difficult to predict the warfarin dose. Polymorphisms in the vitamin K expoxide reductase 1 (VKORC1) and cytochrome P4502C9 (CYP2C9) genes have been reported to influence the warfarin dose. We investigated the effects of the VKORC1 and CYP2C9 genotypes on the warfarin dose in pediatric patients with giant CAAs after KD...
May 8, 2018: Thrombosis Research
https://www.readbyqxmd.com/read/29772534/trapping-methods-for-probing-functional-intermediates-in-nitric-oxide-synthases-and-related-enzymes
#3
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/29767695/molybdenum
#4
Janet A Novotny, Catherine A Peterson
Molybdenum, a trace element essential for micro-organisms, plants, and animals, was discovered in 1778 by a Swedish chemist named Karl Scheele. Initially mistaken for lead, molybdenum was named after the Greek work molybdos, meaning lead-like. In the 1930s, it was recognized that ingestion of forage with high amounts of molybdenum by cattle caused a debilitating condition. In the 1950s, the essentiality of molybdenum was established with the discovery of the first molybdenum-containing enzymes. In humans, only 4 enzymes requiring molybdenum have been identified to date: sulfite oxidase, xanthine oxidase, aldehyde oxidase, and mitochondrial amidoxime-reducing component (mARC)...
May 1, 2018: Advances in Nutrition
https://www.readbyqxmd.com/read/29755560/anti-hypercholesterolemic-effect-of-berbamine-isolated-from-rhizoma-coptidis-in-hypercholesterolemic-zebrafish-induced-by-high-cholesterol-diet
#5
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
#6
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
#7
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
#8
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/29721250/congenital-methemoglobinemia-misdiagnosed-as-polycythemia-vera-case-report-and-review-of-literature
#9
Dina Sameh Soliman, Mohamed Yassin
Methemoglobinemia is a rare overlooked differential diagnosis in patients presented with cyanosis and dyspnea unrelated to cardiopulmonary causes. Our patient is 29 year old Indian non-smoker male, his story started 6 months prior to presentation to our center when he had generalized fatigue and discoloration of hands. He presented with persistent polycythemia with elevated hemoglobin level. The patient was misdiagnosed in another center as polycythemia and treated with Imatinib. The diagnosis of PV was revisited and ruled out in view of negative JAK2, normal erythropoietin level and absence of features of panmyelosis...
March 2, 2018: Hematology Reports
https://www.readbyqxmd.com/read/29719208/functional-importance-of-glutamate-445-and-glutamate-99-in-proton-coupled-electron-transfer-during-oxygen-reduction-by-cytochrome-bd-from-escherichia-coli
#10
Ranjani Murali, Robert B Gennis
The recent X-ray structure of the cytochrome bd respiratory oxygen reductase showed that two of the three heme components, heme d and heme b595 , have glutamic acid as an axial ligand. No other native heme proteins are known to have glutamic acid axial ligands. In this work, site-directed mutagenesis is used to probe the roles of these glutamic acids, E445 and E99 in the E. coli enzyme. It is concluded that neither glutamate is a strong ligand to the heme Fe and they are not the major determinates of heme binding to the protein...
April 29, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29706024/overexpression-of-cyb5r3-and-nqo1-two-nad-producing-enzymes-mimics-aspects-of-caloric-restriction
#11
Alberto Diaz-Ruiz, Michael Lanasa, Joseph Garcia, Hector Mora, Frances Fan, Alejandro Martin-Montalvo, Andrea Di Francesco, Miguel Calvo-Rubio, Andrea Salvador-Pascual, Miguel A Aon, Kenneth W Fishbein, Kevin J Pearson, Jose Manuel Villalba, Placido Navas, Michel Bernier, Rafael de Cabo
Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH-dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b5 reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age-associated diseases...
April 28, 2018: Aging Cell
https://www.readbyqxmd.com/read/29684698/biophysical-characterization-of-aptenodytes-forsteri-cytochrome-p450-aromatase
#12
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/29684324/taxonomic-distribution-structure-function-relationship-and-metabolic-context-of-the-two-families-of-sulfide-dehydrogenases-sqr-and-fcsd
#13
Filipe M Sousa, Juliana G Pereira, Bruno C Marreiros, Manuela M Pereira
Hydrogen sulfide (H2 S) is a versatile molecule with different functions in living organisms: it can work as a metabolite of sulfur and energetic metabolism or as a signaling molecule in higher Eukaryotes. H2 S is also highly toxic since it is able to inhibit heme cooper oxygen reductases, preventing oxidative phosphorylation. Due to the fact that it can both inhibit and feed the respiratory chain, the immediate role of H2 S on energy metabolism crucially relies on its bioavailability, meaning that studying the central players involved in the H2 S homeostasis is key for understanding sulfide metabolism...
April 20, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29679043/identification-and-heterologous-expression-of-the-actinoallolide-biosynthetic-gene-cluster
#14
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/29677198/impact-of-selected-amino-acids-of-hp0377-helicobacter-pylori-thiol-oxidoreductase-on-its-functioning-as-a-ccmg-cytochrome-c-maturation-protein-and-dsb-disulfide-bond-isomerase
#15
Magdalena Joanna Grzeszczuk, Aleksandra Bąk, Anna Marta Banaś, Paweł Urbanowicz, Stanislaw Dunin-Horkawicz, Artur Gieldon, Cezary Czaplewski, Adam Liwo, Elżbieta K Jagusztyn-Krynicka
Helicobacter pylori HP0377 is a thiol oxidoreductase, a member of the CcmG family involved in cytochrome biogenesis, as previously shown by in vitro experiments. In this report, we document that HP0377 also acts in vivo in the cytochrome assembly process in Bacillus subtilis, where it complements the lack of ResA. However, unlike other characterized proteins in this family, HP0377 is a dithiol reductase and isomerase. We elucidated how the amino acid composition of its active site modulates its functionality...
2018: PloS One
https://www.readbyqxmd.com/read/29674492/11beta-hydroxysteroid-dehydrogenase-1-human-tissue-distribution-selective-inhibitor-and-role-in-doxorubicin-metabolism
#16
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/29670639/fdc1-and-leaf-type-ferredoxins-channel-electrons-from-photosystem-i-to-different-downstream-electron-acceptors
#17
Xiaoqian Guan, Shuai Chen, Chia Pao Voon, Kam-Bo Wong, Mikko Tikkanen, Boon L Lim
Plant-type ferredoxins in Arabidopsis transfer electrons from the photosystem I to multiple redox-driven enzymes involved in the assimilation of carbon, nitrogen, and sulfur. Leaf-type ferredoxins also modulate the switch between the linear and cyclic electron routes of the photosystems. Recently, two novel ferredoxin homologs with extra C-termini were identified in the Arabidopsis genome (AtFdC1, AT4G14890; AtFdC2, AT1G32550). FdC1 was considered as an alternative electron acceptor of PSI under extreme ferredoxin-deficient conditions...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29669353/cinobufagin-induces-apoptosis-in-osteosarcoma-cells-via-the-mitochondria-mediated-apoptotic-pathway
#18
Guo Dai, Di Zheng, Weichun Guo, Jian Yang, An-Yuan Cheng
BACKGROUND/AIMS: Osteosarcoma is a common primary malignant bone tumor that mainly occurs in childhood and adolescence. Despite developments in the diagnosis and treatment of osteosarcoma, the prognosis is still very poor. Cinobufagin is an active component in the anti-tumor Chinese medicine called "Chan Su", and we previously revealed that cinobufagin induced apoptosis and reduced the viability of osteosarcoma cells; however, the underlying mechanism remains to be elucidated...
April 13, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29668912/ovine-placental-steroid-synthesis-and-metabolism-in-late-gestation
#19
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
#20
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
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