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Heme iron

Tomas Ganz
Macrophages exert multiple important roles in iron metabolism. As scavengers, splenic and hepatic macrophages phagocytize and degrade senescent and damaged erythrocytes to recycle iron, predominantly for the production of hemoglobin in new erythrocytes. Splenic red pulp macrophages are specialized for iron recycling, with increased expression of proteins for the uptake of hemoglobin, breakdown of heme, and export of iron. Iron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin...
October 2016: Microbiology Spectrum
Stefan Hofbauer, Georg Mlynek, Lisa Milazzo, Dominic Pühringer, Daniel Maresch, Irene Schaffner, Paul G Furtmüller, Giulietta Smulevich, Kristina Djinović-Carugo, Christian Obinger
Heme biosynthesis in Gram positive bacteria follows a recently described coproporphyrin-dependent pathway with HemQ catalyzing the decarboxylation of coproheme to heme b. Here we present the first crystal structure of a HemQ (homopentameric coproproheme-HemQ from Listeria monocytogenes) at 1.69 Å resolution and the conversion of coproheme to heme b followed by UV-vis and resonance Raman spectroscopy as well as mass spectrometry. The ferric 5-coordinated coproheme iron of HemQ is weakly bound by a neutral proximal histidine H174...
October 18, 2016: FEBS Journal
Małgorzata Czerwonka, Andrzej Tokarz
In developed countries, due to high content and bioavailability, red and processed meats are the main sources of iron in the diet. Adequate intake of this nutrient is essential for the proper development and functioning of the human body, and its deficiencies are associated mainly with the occurrence of anemia, which is one of the most widespread nutritional problems in the world. However, excessive intake of iron can be detrimental to health. Studies have shown that high consumption of red meat and its products, and thereby iron, particularly in the form of heme, increases the risk of non-communicable diseases, including cancers, type II diabetes and cardiovascular disease...
October 2, 2016: Meat Science
Yarrow Madrona, Christopher A Waddling, Paul R Ortiz de Montellano
DosS is a sensor in Mycobacterium tuberculosis that differentially responds to O2, NO, and CO, as well as to changes in the redox state of the prosthetic heme iron atom. The ferrous protein and its Fe(II)NO and Fe(II)CO complexes undergo autophosphorylation and subsequently transfer the phosphate group to DosR, a nuclear factor, to activate it. In contrast, autophosphorylation is negligible with the ferric protein and the Fe(II)O2 complex. To clarify the basis for this differential response to gases, we have determined the crystal structures of the NO and COcomplexes of the DosS GAF-A domain, which contains the heme to which the gases bind...
October 8, 2016: Archives of Biochemistry and Biophysics
Gaetano Bergamaschi, Antonio Di Sabatino, Alessandra Pasini, Cristina Ubezio, Filippo Costanzo, Davide Grataroli, Michela Masotti, Costanza Alvisi, Gino R Corazza
BACKGROUND & AIMS: Through inhibition of iron absorption and iron mobilization from tissue stores, hepcidin exerts a negative control on iron homeostasis. Hepcidin, in fact, promotes the degradation of ferroportin (Fpn1), the iron exporter molecule expressed on the membrane of hepatocytes and macrophages, thus preventing iron release from cells to plasma. Hepcidin effects on enterocytes, however, are less clear. Aim of the present study was to further investigate the regulation of iron absorption by hepcidin...
September 30, 2016: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Fabian Cantu Reinhard, Mala Sainna, Pranav Upadhayay, Alex Balan, Devesh Kumar, Simonetta Fornarini, Maria Elisa Crestoni, Samuel de Visser
Cytochrome P450 enzymes are heme containing mono-oxygenases that mainly react through oxygen atom transfer. Specific features of substrate and oxidant that determine the reaction rate constant for oxygen atom transfer are still poorly understood and, therefore, we did a systematic gas-phase study on reactions by iron(IV)-oxo porphyrin cation radical structures with arenes. We present here the first results obtained by using Fourier transform-ion cyclotron resonance mass spectrometry and provide rate constants and product distributions for the assayed reactions...
October 11, 2016: Chemistry: a European Journal
Kyle D Sutherlin, Lei V Liu, Yong-Min Lee, Yeonju Kwak, Yoshitaka Yoda, Makina Saito, Masayuki Kurokuzu, Yasuhiro Kobayashi, Makoto Seto, Lawrence Que, Wonwoo Nam, Edward I Solomon
FeIII-(hydro)peroxy intermediates have been isolated in two classes of mononuclear non-heme Fe enzymes that are important in bioremediation: the Rieske dioxygenases and the extradiol dioxygenases. The binding mode and protonation state of the peroxide moieties in these intermediates are not well defined, due to a lack of vibrational structural data. Nuclear resonance vibrational spectroscopy (NRVS) is an important technique for obtaining vibrational information on these and other intermediates, as it is sensitive to all normal modes with Fe displacement...
October 11, 2016: Journal of the American Chemical Society
Ling Zhang, Jens Ulstrup, Jingdong Zhang
DNA quadruplexes (qs) are a class of "non-canonical" oligonucleotides (OGNs) composed of stacked guanine (G) quartets stabilized by specific cations. Metal porphyrins selectively bind to G-qs complexes to form what is known as DNAzyme, which can exhibit peroxidase and other catalytic activity similar to heme group metalloenzymes. In the present study we investigate the electrochemical properties and the structure of DNAzyme monolayers on single-crystal Au(111)-electrode surfaces using cyclic voltammetry and scanning tunnelling microscopy under electrochemical potential control (in situ STM)...
September 20, 2016: Faraday Discussions
Prasenjit Barman, Abayomi S Faponle, Anil Kumar Vardhaman, Davide Angelone, Anna-Maria Löhr, Wesley R Browne, Peter Comba, Chivukula V Sastri, Sam P de Visser
Reaction bifurcation processes are often encountered in the oxidation of substrates by enzymes and generally lead to a mixture of products. One particular bifurcation process that is common in biology relates to electron transfer versus oxygen atom transfer by high-valent iron(IV)-oxo complexes, which nature uses for the oxidation of metabolites and drugs. In biomimicry and bioremediation, an important reaction relates to the detoxification of ClOx(-) in water, which can lead to a mixture of products through bifurcated reactions...
October 5, 2016: Inorganic Chemistry
Sasha De Henau, Bart P Braeckman
In recent years, moderate levels of reactive oxygen species (ROS) have become recognized as signaling cues that participate at all levels of cellular organization. Globins, with their redox-active heme iron and ubiquitous presence, seem ideally suited to participate in ROS metabolism. Here we comment on our recent findings that show the participation of a globin, GLB-12, in a redox signaling pathway in Caenorhabditis elegans. We found that GLB-12 produces superoxide, a type of ROS, after which this is converted to what appears to be a hydrogen peroxide gradient over the plasma membrane by the activity of intracellular and extracellular superoxide dismutases...
2016: Worm
Jun Sun, Chen Li, Suwen Wang
The current theories of antimalarial mechanism of artemisinin are inadequate to fully explain the observed effects. In our study, "organism-like" formation of Schistosoma hemozoin granules by attaching to and utilizing erythrocytes to form new ones was observed. This indicates that heme iron is transferred from erythrocytes to hemozoin granules during their formation. However, as a disposal product of heme detoxification, these granules are not completely expelled from the Schistosoma gut, but decomposed again between microvilli in the posterior portion of the gut to transfer iron to eggs...
October 3, 2016: Scientific Reports
Julia M Kurth, José A Brito, Jula Reuter, Alexander Flegler, Tobias Koch, Thomas Franke, Eva-Maria Klein, Sam F Rowe, Julea N Butt, Kevin Denkmann, Inês A C Pereira, Margarida Archer, Christiane Dahl
The enzymes of the thiosulfate dehydrogenase (TsdA) family are wide-spread diheme c-type cytochromes. Here, redox carriers were studied mediating the flow of electrons arising from thiosulfate oxidation into respiratory or photosynthetic electron chains. In a number of organisms, including Thiomonas intermedia and Sideroxydans lithotrophicus the tsdA gene is immediately preceded by tsdB encoding for another diheme cytochrome. Spectrophotometric experiments in combination with enzymatic assays in solution showed that TsdB acts as an effective electron acceptor of TsdA in vitro when TsdA and TsdB originate from the same source organism...
September 30, 2016: Journal of Biological Chemistry
Donald Poirier, Jenny Roy, Francisco Cortés-Benítez, Raphaël Dutour
Inhibition of cytochrome P450 1B1 (CYP1B1) represents a promising therapeutic strategy, because it would enable action at three different levels: (1) by inhibiting the formation of mutagenic 4-hydroxy-estradiol, (2) by inhibiting the bioactivation of procarcinogens, and (3) by reducing drug-resistance. Surprisingly, few steroids were reported as inhibitors of CYP1B1. From a screening performed with 90 steroid derivatives, we identified thioestrone (B19) as an inhibitor (IC50=3.4μM) of CYP1B1. Molecular modeling studies showed that the 3-SH group of B19 is closer (3...
September 17, 2016: Bioorganic & Medicinal Chemistry Letters
Ilona K Jóźwik, Flora M Kiss, Łukasz Gricman, Ammar Abdulmughni, Elisa Brill, Josef Zapp, Juergen Pleiss, Rita Bernhardt, Andy-Mark W H Thunnissen
: Cytochrome P450 monooxygenases (P450s) are attractive enzymes for the pharmaceutical industry, in particular, for applications in steroidal drug synthesis. Here, we report a comprehensive functional and structural characterization of CYP109E1, a novel steroid-converting cytochrome P450 enzyme identified from the genome of Bacillus megaterium DSM319. In vitro and whole-cell in vivo turnover experiments, combined with binding assays, revealed that CYP109E1 is able to hydroxylate testosterone at position 16β...
September 30, 2016: FEBS Journal
Marta B Afonso, Pedro M Rodrigues, André L Simão, Dimitry Ofengeim, Tânia Carvalho, Joana D Amaral, Maria M Gaspar, Helena Cortez-Pinto, Rui E Castro, Junying Yuan, Cecília M P Rodrigues
Cholestasis encompasses liver injury and inflammation. Necroptosis, a necrotic cell death pathway regulated by receptor-interacting protein (RIP) 3, may mediate cell death and inflammation in the liver. We aimed to investigate the role of necroptosis in mediating deleterious processes associated with cholestatic liver disease. Hallmarks of necroptosis were evaluated in liver biopsies of primary biliary cholangitis (PBC) patients and in wild-type and RIP3-deficient (RIP3(-/-)) mice subjected to common bile duct ligation (BDL)...
2016: Cell Death & Disease
Kirstine Lindhardt Saederup, Kristian Stoedkilde, Jonas Heilskov Graversen, Claire F Dickson, Anders Etzerodt, Soren Werner Karlskov Hansen, Angela Fago, David Gell, Christian Brix Folsted Andersen, Soren Kragh Moestrup
Hemolysis is a complication in septic infections with Staphylococcus aureus, which utilizes the released hemoglobin (Hb) as an iron source. S. aureus can acquire heme in vitro from Hb by a heme-sequestering mechanism that involves proteins from the S. aureus iron-regulated surface determinant (Isd) system. However, the host has its own mechanism to recapture the free Hb via haptoglobin (Hp) binding and uptake of Hb-Hp by the CD163 receptor in macrophages. It has so far remained unclear how the Isd system competes with this host iron recycling system in situ to obtain the important nutrient...
September 28, 2016: Journal of Biological Chemistry
Baowei Wang, Fansheng Cheng, Shun Gao, Wenhua Ge, Mingai Zhang
Iron deficiency anemia (IDA) is the most common nutritional deficiency worldwide. This deficiency could be solved by preparing stable, edible, and absorbable iron food ingredients using environmentally friendly methods. This study investigated enzymatic hydrolysis and microencapsulation process of goose blood. The physicochemical properties, stabilities of the microencapsulated goose blood hydrolysate (MGBH) and a supplement for rats with IDA were also evaluated. The results showed that the synergetic hydrolytic action of neutrase and alkaline protease significantly increased the heme-releasing efficiency...
February 15, 2017: Food Chemistry
Miriam A Balderas, Chinh Nguyen, Austen Terwilliger, Wendy A Keitel, Angelina Iniguez, Rodrigo Torres, Frederico Palacios, Celia W Goulding, Anthony W Maresso
Bacillus anthracis is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S. licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed - AVA) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multi-shot regimen, recommended boosters, and potential for adverse reactions...
September 19, 2016: Infection and Immunity
Tolunay Beker Aydemir, Catalina Troche, Jinhee Kim, Min-Hyun Kim, Oriana Y Teran, Christiaan Leeuwenburgh, Robert J Cousins
Inflammation and zinc dyshomeostasis are two common hallmarks of aging. A major zinc transporter ZIP14 (slc39a14) is upregulated by proinflammatory stimuli, e.g. interleukin-6. We have evaluated the influence of age on the Zip14 KO phenotype using wild-type (WT) and Zip14 knockout (KO) mice. Aging produced a major increase in serum IL-6 concentrations that was dramatically augmented in the Zip14 KO mice. In keeping with enhanced serum IL-6 concentrations, aging produced tissue-specific increases in zinc concentration of skeletal muscle and white adipose tissue...
September 16, 2016: Experimental Gerontology
Chiharu Yoshimoto, Junko Takahama, Takuya Iwabuchi, Masato Uchikoshi, Hiroshi Shigetomi, Hiroshi Kobayashi
PURPOSE: Heme and iron accumulation due to repeated hemorrhage in endometriosis may contribute to a pivotal role in carcinogenesis. We evaluate the clinical application of MR relaxometry in a series of ovarian endometriosis (OE) and endometriosis-associated ovarian cancer (EAOC). MATERIALS AND METHODS: A prospective study of diagnostic accuracy was conducted among 82 patients (67 OE and 15 EAOC) to compare MR relaxometry and biochemical measurement of cyst fluid total iron concentration...
September 16, 2016: Magnetic Resonance in Medical Sciences: MRMS
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