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Heme iron

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https://www.readbyqxmd.com/read/29458163/dna-adduct-profiling-of-in-vitro-colonic-meat-digests-to-map-red-vs-white-meat-genotoxicity
#1
Lieselot Y Hemeryck, Caroline Rombouts, Ellen De Paepe, Lynn Vanhaecke
The consumption of red meat has been linked to an increased colorectal cancer (CRC) risk. One of the major hypotheses states that heme iron (present in red meat) stimulates the formation of genotoxic N-nitroso compounds (NOCs) and lipid peroxidation products (LPOs). By means of DNA adductomics, chemically induced DNA adduct formation can be mapped in relation to e.g. dietary exposures. In this study, this state-of-the-art methodology was used to investigate alkylation and (lipid per)oxidation induced DNA adduct formation in in vitro red vs...
February 16, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29456553/silencing-of-iron-and-heme-related-genes-revealed-a-paramount-role-of-iron-in-the-physiology-of-the-hematophagous-vector-rhodnius-prolixus
#2
Ana B Walter-Nuno, Mabel L Taracena, Rafael D Mesquita, Pedro L Oliveira, Gabriela O Paiva-Silva
Iron is an essential element for most organisms However, free iron and heme, its complex with protoporphyrin IX, can be extremely cytotoxic, due to the production of reactive oxygen species, eventually leading to oxidative stress. Thus, eukaryotic cells control iron availability by regulating its transport, storage and excretion as well as the biosynthesis and degradation of heme. In the genome of Rhodnius prolixus , the vector of Chagas disease, we identified 36 genes related to iron and heme metabolism We performed a comprehensive analysis of these genes, including identification of homologous genes described in other insect genomes...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29454190/potholing-of-the-hydrophobic-heme-oxygenase-1-western-region-for-the-search-of-potent-and-selective-imidazole-based-inhibitors
#3
Loredana Salerno, Emanuele Amata, Giuseppe Romeo, Agostino Marrazzo, Orazio Prezzavento, Giuseppe Floresta, Valeria Sorrenti, Ignazio Barbagallo, Antonio Rescifina, Valeria Pittalà
Here we report the design, synthesis, and molecular modeling of new potent and selective imidazole-based HO-1 inhibitors in which the imidazole nucleus and the hydrophobic groups are linked by a phenylethanolic spacer. Most of the tested compounds showed a good inhibitor activity with IC 50 values in the low micromolar range, with two of them (1b and 1j) exhibiting also high selectivity toward HO-2. These results were obtained by the idea of potholing the entire volume of the principal hydrophobic western region with an appropriate ligand volume...
February 9, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29452096/the-macrophage-heme-heme-oxygenase-1-system-and-its-role-in-inflammation
#4
REVIEW
Vijith Vijayan, Frank A D T G Wagener, Stephan Immenschuh
Heme oxygenase (HO)-1, the inducible isoform of the heme-degrading enzyme HO, plays a critical role in inflammation and iron homeostasis. Regulatory functions of HO-1 are mediated via the catalytic breakdown of heme, which is an iron-containing tetrapyrrole complex with potential pro-oxidant and pro-inflammatory effects. The HO reaction produces the antioxidant and anti-inflammatory compounds carbon monoxide (CO) and biliverdin, subsequently converted into bilirubin, along with iron, which is reutilized for erythropoiesis...
February 13, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29449016/redox-dependent-axial-ligand-replacement-and-its-functional-significance-in-heme-bound-iron-regulatory-proteins
#5
Mariko Ogura, Ryosuke Endo, Haruto Ishikawa, Yukiko Takeda, Takeshi Uchida, Kazuhiro Iwai, Kazuo Kobayashi, Koichiro Ishimori
Iron regulatory proteins (IRPs), regulators of iron metabolism in mammalian cells, control the translation of proteins involved in iron uptake, storage and utilization by binding to specific iron-responsive element (IRE) sequences of mRNAs. Two homologs of IRPs (IRP1 and IRP2) have a typical heme regulatory motif (HRM), a consensus sequence found in "heme-regulated proteins". However, specific heme binding to HRM has been reported only for IRP2, which is essential for oxidative modification and loss of binding to target mRNAs...
January 9, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29433211/effects-of-cooking-and-food-matrix-on-estimated-mineral-bioavailability-in-mloukhiya-a-mediterranean-dish-based-on-jute-leaves-and-meat
#6
Sondos Njoumi, Sihem Bellagha, Christèle Icard-Vernière, Christian Picq, Marie Josèphe Amiot, Claire Mouquet-Rivier
Traditional Mediterranean plant-based dishes could allow tackling malnutrition while preserving the cultural heritage. To determine the effect of the cooking method on mineral bioavailability, the content in minerals and chelators of Mloukhiya, a Mediterranean dish based on jute leaves (Corchorus olitorius) that contains also meat, was monitored during the whole cooking process. Mineral bioaccessibility was assessed by measuring in vitro dialyzability. Model equation was also used to estimate mineral bioavailability...
March 2018: Food Research International
https://www.readbyqxmd.com/read/29432914/identification-of-the-heme-acquisition-system-in-vibrio-vulnificus-m2799
#7
Hiroaki Kawano, Katsushiro Miyamoto, Megumi Yasunobe, Masahiro Murata, Eri Yamahata, Ryo Yamaguchi, Yuta Miyaki, Takahiro Tsuchiya, Tomotaka Tanabe, Tatsuya Funahashi, Hiroshi Tsujibo
Vibrio vulnificus, the causative agent of serious, often fatal, infections in humans, requires iron for its pathogenesis. As such, it obtains iron via both vulnibactin and heme-mediated iron-uptake systems. In this study, we identified the heme acquisition system in V. vulnificus M2799. The nucleotide sequences of the genes encoding heme receptors HupA and HvtA and the ATP-binding cassette (ABC) transport system proteins HupB, HupC, and HupD were determined, and then used in the construction of deletion mutants developed from a Δics strain, which could not synthesize vulnibactin...
February 9, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29432141/structure-and-function-of-the-cytochrome-p450-peroxygenase-enzymes
#8
REVIEW
Andrew W Munro, Kirsty J McLean, Job L Grant, Thomas M Makris
The cytochromes P450 (P450s or CYPs) constitute a large heme enzyme superfamily, members of which catalyze the oxidative transformation of a wide range of organic substrates, and whose functions are crucial to xenobiotic metabolism and steroid transformation in humans and other organisms. The P450 peroxygenases are a subgroup of the P450s that have evolved in microbes to catalyze the oxidative metabolism of fatty acids, using hydrogen peroxide as an oxidant rather than NAD(P)H-driven redox partner systems typical of the vast majority of other characterized P450 enzymes...
February 6, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29428388/type-ii-flavohemoglobin-of-mycobacterium-smegmatis-oxidizes-d-lactate-and-mediate-electron-transfer
#9
Naveen Thakur, Ashwani Kumar, Kanak L Dikshit
Two distantly related flavohemoglobins (FHbs), MsFHbI and MsFHbII, having crucial differences in their heme and reductase domains, co-exist in Mycobacterium smegmatis. Function of MsFHbI is associated with nitric-oxide detoxification but physiological relevance of MsFHbII remains unknown. This study unravels some unique spectral and functional characteristics of MsFHbII. Unlike conventional type I FHbs, MsFHbII lacks nitric-oxide dioxygenase and NADH oxidase activities but utilizes d-lactate as an electron donor to mediate electron transfer...
February 8, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29427425/dissociation-between-iron-and-heme-biosynthesis-is-largely-accountable-for-respiration-defects-of-shewanella-oneidensis-fur-mutants
#10
Huihui Fu, Lulu Liu, Ziyang Dong, Shupan Guo, Haichun Gao
Iron, a major protein cofactor, is essential for most organisms but can be toxic simultaneously. Iron homeostasis thus has to be effectively maintained under a range of iron regimes. This may be particularly true with Shewanella oneidensis, a representative of dissimilatory metal-reducing bacteria (DMRB) capable of respiring a variety of chemicals as electron acceptors (EAs), including iron ores. Although iron respiration and its regulation have been extensively studied in this bacterium, how iron homeostasis is maintained remains largely unknown...
February 2, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29421865/in-vitro-efficacy-of-free-and-nanoparticle-formulations-of-gallium-iii-meso-tetraphenylporphyrine-against-mycobacterium-avium-and-mycobacterium-abscessus-and-gallium-biodistribution-in-mice
#11
Seoung-Ryoung Choi, Bradley E Britigan, Barbara Switzer, Traci Hoke, David Moran, Prabagaran Narayanasamy
The nontuberculous mycobacterial (NTM) pathogens, M. avium complex (MAC) and M. abscessus, can result in severe pulmonary infections. Current antibiotics confront significant challenges for treatment of these NTM infections due to emerging multidrug-resistance. Thus, development of new antibiotics targeted against these agents is needed. We examined the inhibitory activities of Ga(NO3)3, GaCl3, gallium meso-tetraphenylporphyrin (GaTP) and several derivative nanoparticles (GaNP) against intra- and extracellular M...
February 8, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29421041/characterization-of-a-topologically-unique-oxygenase-from-sphingobium-sp-pnb-capable-of-catalyzing-a-broad-spectrum-of-aromatics
#12
Pratick Khara, Madhumita Roy, Joydeep Chakraborty, Arindam Dutta, Tapan K Dutta
A Rieske non-heme iron ring-hydroxylating oxygenase (RHO) from Sphingobium sp. PNB involved in the initial oxidation of a wide range of low and high molecular weight polycyclic aromatic hydrocarbons (PAHs) was investigated. The RHO was shown to comprise of the gene products of distantly located ahdA1f-ahdA2f, ahdA3 and ahdA4 genes, which encoded the oxygenase α- and β-subunits, ferredoxin and reductase, respectively. In silico structural analysis of AhdA1f revealed a very large substrate-binding pocket, satisfying the spatial requirements to accommodate high molecular weight substrates...
April 2018: Enzyme and Microbial Technology
https://www.readbyqxmd.com/read/29420779/the-mitochondrial-abc-transporter-atm1-plays-a-role-in-iron-metabolism-and-virulence-in-the-human-fungal-pathogen-cryptococcus-neoformans
#13
Eunsoo Do, Seho Park, Ming-Hui Li, Jia-Mei Wang, Chen Ding, James W Kronstad, Won Hee Jung
Iron-sulfur clusters (ISC) are indispensable cofactors for essential enzymes in various cellular processes. In the model yeast Saccharomyces cerevisiae, the precursor of ISCs is exported from mitochondria via a mitochondrial ABC transporter Atm1 and used for cytosolic and nuclear ISC protein assembly. Although iron homeostasis has been implicated in the virulence of the human fungal pathogen Cryptococcus neoformans, the key components of the ISC biosynthesis pathway need to be fully elucidated. In the current study, a homolog of S...
October 9, 2017: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29419812/attenuation-of-glucose-induced-myoglobin-glycation-and-the-formation-of-advanced-glycation-end-products-ages-by-r-%C3%AE-lipoic-acid-in-vitro
#14
Hardik Ghelani, Valentina Razmovski-Naumovski, Rajeswara Rao Pragada, Srinivas Nammi
High-carbohydrate containing diets have become a precursor to glucose-mediated protein glycation which has been linked to an increase in diabetic and cardiovascular complications. The aim of the present study was to evaluate the protective effect of (R)-α-lipoic acid (ALA) against glucose-induced myoglobin glycation and the formation of advanced glycation end products (AGEs) in vitro. METHODS: The effect of ALA on myoglobin glycation was determined via the formation of AGEs fluorescence intensity, iron released from the heme moiety of myoglobin and the level of fructosamine...
February 8, 2018: Biomolecules
https://www.readbyqxmd.com/read/29414780/decarboxylation-involving-a-ferryl-propionate-and-a-tyrosyl-group-in-a-radical-relay-yields-heme-em-b-em
#15
Bennett R Streit, Arianna I Celis, Garrett C Moraski, Krista Shisler, Eric M Shepard, Kenton R Rodgers, Gudrun S Lukat-Rodgers, Jennifer L DuBois
The H2O2-dependent oxidative decarboxylation of coproheme III is the final step in the biosynthesis of heme<em> b</em> in many microbes. However, the coproheme decarboxylase reaction mechanism is unclear. The structure of the decarboxylase in complex with coproheme III suggested that the substrate iron, reactive propionates, and an active-site tyrosine convey a net 2e-/2H+ from each propionate to an activated form of H2O2 Time-resolved EPR spectroscopy revealed that Tyr-145 forms a radical species within 30 sec of the reaction of the enzyme-coproheme complex with H2O2 This radical disappeared over the next 270 sec, consistent with a catalytic intermediate...
February 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29409696/fur-regulation-of-staphylococcus-aureus-heme-oxygenases-is-required-for-heme-homeostasis
#16
Lisa J Lojek, Allison J Farrand, Andy Weiss, Eric P Skaar
Heme is a cofactor that is essential for cellular respiration and for the function of many enzymes. If heme levels become too low within the cell, S. aureus switches from producing energy via respiration to producing energy by fermentation. S. aureus encodes two heme oxygenases, IsdI and IsdG, which cleave the porphyrin heme ring releasing iron for use as a nutrient source. Both isdI and isdG are only expressed under low iron conditions and are regulated by the canonical Ferric Uptake Regulator (Fur). Here we demonstrate that unregulated expression of isdI and isdG within S...
February 1, 2018: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/29398549/role-of-cadc-and-cadd-in-the-2-4-dichlorophenoxyacetic-acid-oxygenase-system-of-sphingomonas-agrestis-58-1
#17
Kumiko Kijima, Hajime Mita, Mitsuyasu Kawakami, Kei Amada
In the present study, we confirm that 2,4-dichlorophenoxyacetic acid (2,4-D) oxygenase from Sphingomonas agrestis 58-1 belongs to the family of Rieske non-heme iron aromatic ring-hydroxylating oxygenases, which comprise a core enzyme (oxygenase), ferredoxin, and oxidoreductase. It has previously been shown that cadAB genes are necessary for the conversion of 2,4-D to 2,4-dichlorophenol; however, the respective roles of ferredoxin and oxidoreductase in the 2,4-D oxygenase system from S. agrestis 58-1 remain unknown...
February 2, 2018: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/29394034/iron-and-its-role-in-cancer-defense-a-double-edged-sword
#18
Frank Thévenod
Iron (Fe) is an essential metal, vital for biological functions, including electron transport, DNA synthesis, detoxification, and erythropoiesis that all contribute to metabolism, cell growth, and proliferation. Interactions between Fe and O2 can result in the generation of reactive oxygen species (ROS), which is based on the ability of Fe to redox cycle. Excess Fe may cause oxidative damage with ensuing cell death, but DNA damage may also lead to permanent mutations. Hence Fe is carcinogenic and may initiate tumor formation and growth, and also nurture the tumor microenvironment and metastasis...
February 5, 2018: Metal Ions in Life Sciences
https://www.readbyqxmd.com/read/29382736/pseudomonas-aeruginosa-algr-phosphorylation-status-differentially-regulates-pyocyanin-and-pyoverdine-production
#19
Alexander S Little, Yuta Okkotsu, Alexandria A Reinhart, F Heath Damron, Mariette Barbier, Brandon Barrett, Amanda G Oglesby-Sherrouse, Joanna B Goldberg, William L Cody, Michael J Schurr, Michael L Vasil, Michael J Schurr
Pseudomonas aeruginosa employs numerous, complex regulatory elements to control expression of its many virulence systems. The P. aeruginosa AlgZR two-component regulatory system controls the expression of several crucial virulence phenotypes. We recently determined, through transcriptomic profiling of a PAO1 ΔalgR mutant strain compared to wild-type PAO1, that algZR and hemCD are cotranscribed and show differential iron-dependent gene expression. Previous expression profiling was performed in strains without algR and revealed that AlgR acts as either an activator or repressor, depending on the gene...
January 30, 2018: MBio
https://www.readbyqxmd.com/read/29381787/red-meat-consumption-and-risk-of-cardiovascular-diseases-is-increased-iron-load-a-possible-link
#20
Daniel A Quintana Pacheco, Disorn Sookthai, Clemens Wittenbecher, Mirja E Graf, Ruth Schübel, Theron Johnson, Verena Katzke, Paula Jakszyn, Rudolf Kaaks, Tilman Kühn
Background: High iron load and red meat consumption could increase the risk of cardiovascular diseases (CVDs). As red meat is the main source of heme iron, which is in turn a major determinant of increased iron load, adverse cardiometabolic effects of meat consumption could be mediated by increased iron load. Objective: The object of the study was to assess whether associations between red meat consumption and CVD risk are mediated by iron load in a population-based human study...
January 1, 2018: American Journal of Clinical Nutrition
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