1.
BRENDA
–
BRENDA is an information system representing one of the most comprehensive enzyme repositories. It is a resource that comprises molecular and biochemical information on enzymes that have been classified by the IUBMB. Every classified enzyme is characterized with respect to its catalyzed biochemical reaction, kinetic properties of the corresponding reactants are described in detail. BRENDA contains enzyme-specific data manually extracted from scientific literature and additional data derived from automatic information retrieval methods such as text mining. It provides a user interface that allows a convenient and sophisticated access to the data. BRENDA was founded in 1987 at the former German National Research Centre for Biotechnology in Braunschweig and was published as a series of books. Its name was originally an acronym for the Braunschweig Enzyme Database, from 1996 to 2007, BRENDA was located at the University of Cologne. There, BRENDA developed into a publicly accessible enzyme information system, in 2007, BRENDA returned to Braunschweig. Currently, BRENDA is maintained and further developed at the Department of Bioinformatics, a major update of the data in BRENDA is performed twice a year. Besides the upgrade of its content, improvements of the interface are also incorporated into the BRENDA database. The latest update was performed in January 2015, Database, The database contains more than 40 data fields with enzyme-specific information on more than 7000 EC numbers that are classified according to the IUBMB. Currently, BRENDA contains manually annotated data from over 140,000 different scientific articles, each enzyme entry is clearly linked to at least one literature reference, to its source organism, and, where available, to the protein sequence of the enzyme. An important part of BRENDA represent the more than 110,000 enzyme ligands, the term ligand is used in this context to all low molecular weight compounds which interact with enzymes. These include not only metabolites of primary metabolism, co-substrates or cofactors, the origin of these molecules ranges from naturally occurring antibiotics to synthetic compounds that have been synthesized for the development of drugs or pesticides. Furthermore, cross-references to external resources such as sequence and 3D-structure databases. Extensions, Since 2006, the data in BRENDA is supplemented with information extracted from the literature by a co-occurrence based text mining approach. For this purpose, four text-mining repositories FRENDA, AMENDA, DRENDA and KENDA were introduced and these text-mining results were derived from the titles and abstracts of all articles in the literature database PubMed. Data access, There are several tools to access to the data in BRENDA
2.
MetaCyc
–
The MetaCyc database contains extensive information on metabolic pathways and enzymes from many organisms. MetaCyc is also used in engineering and metabolomics research. MetaCyc contains extensive data on individual enzymes, describing their subunit structure, cofactors, activators and inhibitors, substrate specificity, MetaCyc data on reactions includes predicted atom mappings that describe the correspondence between atoms in the reactant compounds and the product compounds. It also provides enzyme mini-reviews and literature references, MetaCyc data on metabolites includes chemical structures, predicted Gibbs free energies of formation, and links to external databases
3.
Protein Data Bank
–
The Protein Data Bank is a crystallographic database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The PDB is overseen by a called the Worldwide Protein Data Bank. The PDB is a key resource in areas of structural biology, most major scientific journals, and some funding agencies, now require scientists to submit their structure data to the PDB. Many other databases use protein structures deposited in the PDB, for example, SCOP and CATH classify protein structures, while PDBsum provides a graphic overview of PDB entries using information from other sources, such as Gene ontology. By 1971, one of Meyers programs, SEARCH, enabled researchers to access information from the database to study protein structures offline. SEARCH was instrumental in enabling networking, thus marking the beginning of the PDB. Upon Hamiltons death in 1973, Tom Koeztle took over direction of the PDB for the subsequent 20 years, in January 1994, Joel Sussman of Israels Weizmann Institute of Science was appointed head of the PDB. In October 1998, the PDB was transferred to the Research Collaboratory for Structural Bioinformatics, the new director was Helen M. Berman of Rutgers University. In 2003, with the formation of the wwPDB, the PDB became an international organization, the founding members are PDBe, RCSB, and PDBj. Each of the four members of wwPDB can act as deposition, data processing, the data processing refers to the fact that wwPDB staff review and annotate each submitted entry. The data are automatically checked for plausibility. The PDB database is updated weekly, likewise, the PDB holdings list is also updated weekly. As of 14 March 2017, the breakdown of current holdings is as follows,103,514 structures in the PDB have a structure factor file,9,057 structures have an NMR restraint file. 2,826 structures in the PDB have a chemical shifts file, therefore, the final conformation of the protein is obtained, in the latter case, by solving a distance geometry problem. A few proteins are determined by cryo-electron microscopy, the significance of the structure factor files, mentioned above, is that, for PDB structures determined by X-ray diffraction that have a structure file, the electron density map may be viewed. The data of such structures is stored on the electron density server, however, since 2007, the rate of accumulation of new protein structures appears to have plateaued. The file format used by the PDB was called the PDB file format. This original format was restricted by the width of computer punch cards to 80 characters per line, around 1996, the macromolecular Crystallographic Information file format, mmCIF, which is an extension of the CIF format started to be phased in
4.
PubMed
–
PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez system of information retrieval, from 1971 to 1997, MEDLINE online access to the MEDLARS Online computerized database primarily had been through institutional facilities, such as university libraries. PubMed, first released in January 1996, ushered in the era of private, free, home-, the PubMed system was offered free to the public in June 1997, when MEDLINE searches via the Web were demonstrated, in a ceremony, by Vice President Al Gore. Information about the journals indexed in MEDLINE, and available through PubMed, is found in the NLM Catalog. As of 5 January 2017, PubMed has more than 26.8 million records going back to 1966, selectively to the year 1865, and very selectively to 1809, about 500,000 new records are added each year. As of the date,13.1 million of PubMeds records are listed with their abstracts. In 2016, NLM changed the system so that publishers will be able to directly correct typos. Simple searches on PubMed can be carried out by entering key aspects of a subject into PubMeds search window, when a journal article is indexed, numerous article parameters are extracted and stored as structured information. Such parameters are, Article Type, Secondary identifiers, Language, publication type parameter enables many special features. As these clinical girish can generate small sets of robust studies with considerable precision, since July 2005, the MEDLINE article indexing process extracts important identifiers from the article abstract and puts those in a field called Secondary Identifier. The secondary identifier field is to store numbers to various databases of molecular sequence data, gene expression or chemical compounds. For clinical trials, PubMed extracts trial IDs for the two largest trial registries, ClinicalTrials. gov and the International Standard Randomized Controlled Trial Number Register, a reference which is judged particularly relevant can be marked and related articles can be identified. If relevant, several studies can be selected and related articles to all of them can be generated using the Find related data option, the related articles are then listed in order of relatedness. To create these lists of related articles, PubMed compares words from the title and abstract of each citation, as well as the MeSH headings assigned, using a powerful word-weighted algorithm. The related articles function has been judged to be so precise that some researchers suggest it can be used instead of a full search, a strong feature of PubMed is its ability to automatically link to MeSH terms and subheadings. Examples would be, bad breath links to halitosis, heart attack to myocardial infarction, where appropriate, these MeSH terms are automatically expanded, that is, include more specific terms. Terms like nursing are automatically linked to Nursing or Nursing and this important feature makes PubMed searches automatically more sensitive and avoids false-negative hits by compensating for the diversity of medical terminology. The My NCBI area can be accessed from any computer with web-access, an earlier version of My NCBI was called PubMed Cubby
5.
National Center for Biotechnology Information
–
The National Center for Biotechnology Information is part of the United States National Library of Medicine, a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper, the NCBI houses a series of databases relevant to biotechnology and biomedicine and is an important resource for bioinformatics tools and services. Major databases include GenBank for DNA sequences and PubMed, a database for the biomedical literature. Other databases include the NCBI Epigenomics database, all these databases are available online through the Entrez search engine. NCBI is directed by David Lipman, one of the authors of the BLAST sequence alignment program. He also leads a research program, including groups led by Stephen Altschul, David Landsman, Eugene Koonin, John Wilbur, Teresa Przytycka. NCBI is listed in the Registry of Research Data Repositories re3data. org, NCBI has had responsibility for making available the GenBank DNA sequence database since 1992. GenBank coordinates with individual laboratories and other databases such as those of the European Molecular Biology Laboratory. Since 1992, NCBI has grown to other databases in addition to GenBank. The NCBI assigns a unique identifier to each species of organism, the NCBI has software tools that are available by WWW browsing or by FTP. For example, BLAST is a sequence similarity searching program, BLAST can do sequence comparisons against the GenBank DNA database in less than 15 seconds. RAG2/IL2RG The NCBI Bookshelf is a collection of freely accessible, downloadable, some of the books are online versions of previously published books, while others, such as Coffee Break, are written and edited by NCBI staff. BLAST is a used for calculating sequence similarity between biological sequences such as nucleotide sequences of DNA and amino acid sequences of proteins. BLAST is a tool for finding sequences similar to the query sequence within the same organism or in different organisms. It searches the query sequence on NCBI databases and servers and post the results back to the browser in chosen format. Input sequences to the BLAST are mostly in FASTA or Genbank format while output could be delivered in variety of such as HTML, XML formatting. HTML is the output format for NCBIs web-page. Entrez is both indexing and retrieval system having data from sources for biomedical research
6.
Enzyme
–
Enzymes /ˈɛnzaɪmz/ are macromolecular biological catalysts. Enzymes accelerate, or catalyze, chemical reactions, the molecules at the beginning of the process upon which enzymes may act are called substrates and the enzyme converts these into different molecules, called products. Almost all metabolic processes in the cell need enzymes in order to occur at rates fast enough to sustain life, the set of enzymes made in a cell determines which metabolic pathways occur in that cell. The study of enzymes is called enzymology, enzymes are known to catalyze more than 5,000 biochemical reaction types. Most enzymes are proteins, although a few are catalytic RNA molecules, enzymes specificity comes from their unique three-dimensional structures. Like all catalysts, enzymes increase the rate of a reaction by lowering its activation energy, some enzymes can make their conversion of substrate to product occur many millions of times faster. An extreme example is orotidine 5-phosphate decarboxylase, which allows a reaction that would take millions of years to occur in milliseconds. Chemically, enzymes are like any catalyst and are not consumed in chemical reactions, enzymes differ from most other catalysts by being much more specific. Enzyme activity can be affected by other molecules, inhibitors are molecules that decrease enzyme activity, many drugs and poisons are enzyme inhibitors. An enzymes activity decreases markedly outside its optimal temperature and pH, some enzymes are used commercially, for example, in the synthesis of antibiotics. French chemist Anselme Payen was the first to discover an enzyme, diastase and he wrote that alcoholic fermentation is an act correlated with the life and organization of the yeast cells, not with the death or putrefaction of the cells. In 1877, German physiologist Wilhelm Kühne first used the term enzyme, the word enzyme was used later to refer to nonliving substances such as pepsin, and the word ferment was used to refer to chemical activity produced by living organisms. Eduard Buchner submitted his first paper on the study of yeast extracts in 1897, in a series of experiments at the University of Berlin, he found that sugar was fermented by yeast extracts even when there were no living yeast cells in the mixture. He named the enzyme that brought about the fermentation of sucrose zymase, in 1907, he received the Nobel Prize in Chemistry for his discovery of cell-free fermentation. Following Buchners example, enzymes are usually named according to the reaction they carry out, the biochemical identity of enzymes was still unknown in the early 1900s. Sumner showed that the enzyme urease was a protein and crystallized it. These three scientists were awarded the 1946 Nobel Prize in Chemistry, the discovery that enzymes could be crystallized eventually allowed their structures to be solved by x-ray crystallography. This high-resolution structure of lysozyme marked the beginning of the field of structural biology, an enzymes name is often derived from its substrate or the chemical reaction it catalyzes, with the word ending in -ase
7.
Catalysis
–
Catalysis is the increase in the rate of a chemical reaction due to the participation of an additional substance called a catalyst. In most cases, reactions occur faster with a catalyst because they require less activation energy, furthermore, since they are not consumed in the catalyzed reaction, catalysts can continue to act repeatedly. Often only tiny amounts are required in principle, in the presence of a catalyst, less free energy is required to reach the transition state, but the total free energy from reactants to products does not change. A catalyst may participate in multiple chemical transformations, the effect of a catalyst may vary due to the presence of other substances known as inhibitors or poisons or promoters. Catalyzed reactions have an activation energy than the corresponding uncatalyzed reaction, resulting in a higher reaction rate at the same temperature. However, the mechanics of catalysis is complex. Usually, the catalyst participates in this slowest step, and rates are limited by amount of catalyst, in heterogeneous catalysis, the diffusion of reagents to the surface and diffusion of products from the surface can be rate determining. A nanomaterial-based catalyst is an example of a heterogeneous catalyst, analogous events associated with substrate binding and product dissociation apply to homogeneous catalysts. Although catalysts are not consumed by the reaction itself, they may be inhibited, deactivated, in heterogeneous catalysis, typical secondary processes include coking where the catalyst becomes covered by polymeric side products. Additionally, heterogeneous catalysts can dissolve into the solution in a system or sublimate in a solid–gas system. The production of most industrially important chemicals involves catalysis, similarly, most biochemically significant processes are catalysed. Research into catalysis is a field in applied science and involves many areas of chemistry, notably organometallic chemistry. Catalysis is relevant to aspects of environmental science, e. g. the catalytic converter in automobiles. Many transition metals and transition metal complexes are used in catalysis as well, Catalysts called enzymes are important in biology. A catalyst works by providing a reaction pathway to the reaction product. The rate of the reaction is increased as this route has a lower activation energy than the reaction route not mediated by the catalyst. The disproportionation of hydrogen peroxide creates water and oxygen, as shown below,2 H2O2 →2 H2O + O2 This reaction is preferable in the sense that the reaction products are more stable than the starting material, though the uncatalysed reaction is slow. In fact, the decomposition of hydrogen peroxide is so slow that hydrogen peroxide solutions are commercially available and this reaction is strongly affected by catalysts such as manganese dioxide, or the enzyme peroxidase in organisms
8.
Chemical reaction
–
A chemical reaction is a process that leads to the transformation of one set of chemical substances to another. Nuclear chemistry is a sub-discipline of chemistry that involves the reactions of unstable. The substance initially involved in a reaction are called reactants or reagents. Chemical reactions are characterized by a chemical change, and they yield one or more products. Reactions often consist of a sequence of individual sub-steps, the elementary reactions. Chemical reactions are described with chemical equations, which present the starting materials, end products. Chemical reactions happen at a characteristic reaction rate at a given temperature, typically, reaction rates increase with increasing temperature because there is more thermal energy available to reach the activation energy necessary for breaking bonds between atoms. Reactions may proceed in the forward or reverse direction until they go to completion or reach equilibrium, Reactions that proceed in the forward direction to approach equilibrium are often described as spontaneous, requiring no input of free energy to go forward. Non-spontaneous reactions require input of energy to go forward. Different chemical reactions are used in combinations during chemical synthesis in order to obtain a desired product, in biochemistry, a consecutive series of chemical reactions form metabolic pathways. These reactions are catalyzed by protein enzymes. Chemical reactions such as combustion in fire, fermentation and the reduction of ores to metals were known since antiquity, in the Middle Ages, chemical transformations were studied by Alchemists. They attempted, in particular, to lead into gold, for which purpose they used reactions of lead. The process involved heating of sulfate and nitrate minerals such as sulfate, alum. In the 17th century, Johann Rudolph Glauber produced hydrochloric acid and sodium sulfate by reacting sulfuric acid, further optimization of sulfuric acid technology resulted in the contact process in the 1880s, and the Haber process was developed in 1909–1910 for ammonia synthesis. From the 16th century, researchers including Jan Baptist van Helmont, Robert Boyle, the phlogiston theory was proposed in 1667 by Johann Joachim Becher. It postulated the existence of an element called phlogiston, which was contained within combustible bodies. This proved to be false in 1785 by Antoine Lavoisier who found the explanation of the combustion as reaction with oxygen from the air
9.
(E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate
–
-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate is an intermediate of the MEP pathway of isoprenoid biosynthesis. The enzyme HMB-PP synthase catalyzes the conversion of 2-C-methyl-D-erythritol 2, 4-cyclodiphosphate into HMB-PP, HMB-PP is then converted further to isopentenyl pyrophosphate and dimethylallyl pyrophosphate by HMB-PP reductase. HMB-PP is a metabolite in most pathogenic bacteria including Mycobacterium tuberculosis as well as in malaria parasites. HMB-PP is the activator for human Vγ9/Vδ2 T cells, the major γδ T cell population in peripheral blood. With a bioactivity of 0.1 nM it is 10, 000-10,000,000 times more potent than any other natural compound, HMB-PP functions in this capacity by binding the B30.2 domain of BTN3A1. 4-hydroxy-3-methylbut-2-enyl pyrophosphate at the US National Library of Medicine Medical Subject Headings
10.
Ferredoxin
–
Ferredoxins are iron-sulfur proteins that mediate electron transfer in a range of metabolic reactions. The term ferredoxin was coined by D. C, wharton of the DuPont Co. and applied to the iron protein first purified in 1962 by Mortenson, Valentine, and Carnahan from the anaerobic bacterium Clostridium pasteurianum. Another redox protein, isolated from spinach chloroplasts, was termed chloroplast ferredoxin, the chloroplast ferredoxin is involved in both cyclic and non-cyclic photophosphorylation reactions of photosynthesis. In non-cyclic photophosphorylation, ferredoxin is the last electron acceptor thus reducing the enzyme NADP+ reductase and it accepts electrons produced from sunlight-excited chlorophyll and transfers them to the enzyme ferredoxin, NADP+ oxidoreductase EC1.18.1.2. Ferredoxins are small proteins containing iron and sulfur atoms organized as iron-sulfur clusters and these biological capacitors can accept or discharge electrons, with the effect of a change in the oxidation state of the iron atoms between +2 and +3. In this way, ferredoxin acts as a transfer agent in biological redox reactions. Other bioinorganic electron transport systems include rubredoxins, cytochromes, blue copper proteins, ferredoxins can be classified according to the nature of their iron-sulfur clusters and by sequence similarity. Members of the 2Fe-2S ferredoxin family have a core structure consisting of beta-alpha-beta, which includes putidaredoxin, terpredoxin. They are proteins of around one hundred amino acids with four conserved cysteine residues to which the 2Fe-2S cluster is ligated, one group of ferredoxins, originally found in chloroplast membranes, has been termed chloroplast-type or plant-type. Its active center is a cluster, where the atoms are tetrahedrally coordinated both by inorganic sulfur atoms and by sulfurs of four conserved cysteine residues. In hydroxylating bacterial dioxygenase systems, they serve as intermediate electron-transfer carriers between reductase flavoproteins and oxygenase, although the physiological role of this ferredoxin remains unclear, a strong and specific interaction of Cp2FeFd with the molybdenum-iron protein of nitrogenase has been revealed. Homologous ferredoxins from Azotobacter vinelandii and Aquifex aeolicus have been characterized, the crystal structure of AaFd has been solved. The structure of AaFd monomer is different from other Fe2S2 ferredoxins, the fold belongs to the α+β class, with first four β-strands and two α-helices adopting a variant of the thioredoxin fold. Adrenodoxin is expressed in mammals including humans, the human variant of adrenodoxin is referred to as ferredoxin 1. Adrenodoxin, putidaredoxin, and terpredoxin are soluble Fe2S2 proteins that act as electron carriers. In mitochondrial monooxygenase systems, adrenodoxin transfers an electron from NADPH, in bacteria, putidaredoxin and terpredoxin serve as electron carriers between corresponding NADH-dependent ferredoxin reductases and soluble P450s. The exact functions of members of this family are not known. Despite low sequence similarity between adrenodoxin-type and plant-type ferredoxins, the two classes have a similar folding topology, ferredoxin-1 in humans participates in the synthesis of thyroid hormones
11.
Terpenoid
–
Most are multicyclic structures that differ from one another not only in functional groups but also in their basic carbon skeletons. These lipids can be found in all classes of living things, about 60% of known natural products are terpenoids. Plant terpenoids are used extensively for their qualities and play a role in traditional herbal remedies. Terpenoids contribute to the scent of eucalyptus, the flavors of cinnamon, cloves, and ginger, the color in sunflowers. The steroids and sterols in animals are produced from terpenoid precursors. Sometimes terpenoids are added to proteins, e. g. to enhance their attachment to the cell membrane, terpenes are hydrocarbons resulting from the condensation of several 5-carbon isoprene units. The isoprene unit has the formula CH2=CCH=CH2, terpenoids can be thought of as modified terpenes, wherein methyl groups have been moved or removed, or oxygen atoms added. The Salkowski test can be used to identify the presence of terpenoids, meroterpenes are any compound, including many natural products, having a partial terpenoid structure. There are two pathways that create terpenoids, Many organisms manufacture terpenoids through the HMG-CoA reductase pathway. The reactions take place in the cytosol, the pathway was discovered in the 1950s. It was discovered in the late 1980s, pyruvate and glyceraldehyde 3-phosphate are converted by DOXP synthase to 1-deoxy-D-xylulose 5-phosphate, and by DOXP reductase to 2-C-methyl-D-erythritol 4-phosphate. IPP and DMAPP are the end-products in either pathway, and are the precursors of isoprene, monoterpenoids, diterpenoids, carotenoids, chlorophylls, synthesis of all higher terpenoids proceeds via formation of geranyl pyrophosphate, farnesyl pyrophosphate, and geranylgeranyl pyrophosphate. Although both pathways, MVA and MEP, are exclusive in most organisms, interactions between them have been reported in plants and few bacteria species. It is a material for synthesis of vitamin A. List of antioxidants in food List of phytochemicals in food Nutrition Phytochemistry Secondary metabolites IUPAC nomenclature of terpenoids
12.
PubMed Identifier
–
PubMed is a free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez system of information retrieval, from 1971 to 1997, MEDLINE online access to the MEDLARS Online computerized database primarily had been through institutional facilities, such as university libraries. PubMed, first released in January 1996, ushered in the era of private, free, home-, the PubMed system was offered free to the public in June 1997, when MEDLINE searches via the Web were demonstrated, in a ceremony, by Vice President Al Gore. Information about the journals indexed in MEDLINE, and available through PubMed, is found in the NLM Catalog. As of 5 January 2017, PubMed has more than 26.8 million records going back to 1966, selectively to the year 1865, and very selectively to 1809, about 500,000 new records are added each year. As of the date,13.1 million of PubMeds records are listed with their abstracts. In 2016, NLM changed the system so that publishers will be able to directly correct typos. Simple searches on PubMed can be carried out by entering key aspects of a subject into PubMeds search window, when a journal article is indexed, numerous article parameters are extracted and stored as structured information. Such parameters are, Article Type, Secondary identifiers, Language, publication type parameter enables many special features. As these clinical girish can generate small sets of robust studies with considerable precision, since July 2005, the MEDLINE article indexing process extracts important identifiers from the article abstract and puts those in a field called Secondary Identifier. The secondary identifier field is to store numbers to various databases of molecular sequence data, gene expression or chemical compounds. For clinical trials, PubMed extracts trial IDs for the two largest trial registries, ClinicalTrials. gov and the International Standard Randomized Controlled Trial Number Register, a reference which is judged particularly relevant can be marked and related articles can be identified. If relevant, several studies can be selected and related articles to all of them can be generated using the Find related data option, the related articles are then listed in order of relatedness. To create these lists of related articles, PubMed compares words from the title and abstract of each citation, as well as the MeSH headings assigned, using a powerful word-weighted algorithm. The related articles function has been judged to be so precise that some researchers suggest it can be used instead of a full search, a strong feature of PubMed is its ability to automatically link to MeSH terms and subheadings. Examples would be, bad breath links to halitosis, heart attack to myocardial infarction, where appropriate, these MeSH terms are automatically expanded, that is, include more specific terms. Terms like nursing are automatically linked to Nursing or Nursing and this important feature makes PubMed searches automatically more sensitive and avoids false-negative hits by compensating for the diversity of medical terminology. The My NCBI area can be accessed from any computer with web-access, an earlier version of My NCBI was called PubMed Cubby
13.
Superoxide
–
A superoxide, also known by the obsolete name hyperoxide, is a compound that contains the superoxide anion with the chemical formula O−2. The systematic name of the anion is dioxide, the reactive oxygen anion superoxide is particularly important as the product of the one-electron reduction of dioxygen O2, which occurs widely in nature. Both dioxygen and the anion are free radicals that exhibit paramagnetism. Superoxides are compounds in which the number of oxygen is − 1⁄2. The O–O bond distance in O−2 is 1.33 Å, the salts CsO2, RbO2, KO2, and NaO2 are prepared by the direct reaction of O2 with the respective alkali metal. The overall trend corresponds to a reduction in the order from 2, to 1.5. The alkali salts of O−2 are orange-yellow in color and quite stable, superoxides are also used in firefighters oxygen tanks in order to provide a readily available source of oxygen. In this process O−2 acts as a Brønsted base, initially forming the radical HO2·. But the pKa of its conjugate acid, hydrogen superoxide, is 4.88 so that at neutral pH7 all but 0. 3% of superoxide is in the anionic form, O−2. Potassium superoxide can be dissolved in dimethyl sulfoxide and is stable as long as protons are not available, superoxide can also be generated in aprotic solvents by cyclic voltammetry. Superoxide is biologically quite toxic and is deployed by the system to kill invading microorganisms. In phagocytes, superoxide is produced in quantities by the enzyme NADPH oxidase for use in oxygen-dependent killing mechanisms of invading pathogens. In turn, micro-organisms genetically engineered to lack superoxide dismutase lose virulence, superoxide is also deleterious when produced as a byproduct of mitochondrial respiration, as well as several other enzymes, for example xanthine oxidase. Because superoxide is toxic, nearly all living in the presence of oxygen contain isoforms of the superoxide-scavenging enzyme superoxide dismutase. SOD is an efficient enzyme, it catalyzes the neutralization of superoxide nearly as quickly as the two can diffuse together spontaneously in solution. Other proteins that can be oxidized and reduced by superoxide have weak SOD-like activity. Genetic inactivation of SOD produces deleterious phenotypes in organisms ranging from bacteria to mice and have provided important clues as to the mechanisms of toxicity of superoxide in vivo, yeast lacking both mitochondrial and cytosolic SOD grow very poorly in air, but quite well under anaerobic conditions. Absence of cytosolic SOD causes an increase in mutagenesis and genomic instability
14.
Superoxide dismutase
–
Superoxide dismutase is an enzyme that alternately catalyzes the dismutation of the superoxide radical into either ordinary molecular oxygen or hydrogen peroxide. Superoxide is produced as a by-product of oxygen metabolism and, if not regulated, hydrogen peroxide is also damaging and is degraded by other enzymes such as catalase. Thus, SOD is an important antioxidant defense in all living cells exposed to oxygen. One exception is Lactobacillus plantarum and related lactobacilli, which use a different mechanism to prevent damage from reactive, where M = Cu, Mn, Fe, Ni. In a series of reactions, the oxidation state and the charge of the metal cation oscillates between n and n+1, +1 and +2 for Cu, or +2 and +3 for the other metals. Irwin Fridovich and Joe McCord at Duke University discovered the activity of superoxide dismutase in 1968. SODs were previously known as a group of metalloproteins with unknown function, for example, likewise, Brewer identified a protein that later became known as superoxide dismutase as an indophenol oxidase by protein analysis of starch gels using the phenazine-tetrazolium technique. There are three families of superoxide dismutase, depending on the protein fold and the metal cofactor, the Cu/Zn type, Fe and Mn types. Copper and zinc – most commonly used by eukaryotes, including humans, the cytosols of virtually all eukaryotic cells contain an SOD enzyme with copper and zinc. For example, Cu-Zn-SOD available commercially is normally purified from red blood cells. The bovine Cu-Zn enzyme is a homodimer of molecular weight 32,500 and it was the first SOD whose atomic-detail crystal structure was solved, in 1975. It is an 8-stranded Greek key beta-barrel, with the site held between the barrel and two surface loops. The two subunits are tightly joined back-to-back, mostly by hydrophobic and some electrostatic interactions, the ligands of the copper and zinc are six histidine and one aspartate side-chains, one histidine is bound between the two metals. Fe-SOD can also be found in the chloroplasts of plants, the 3D structures of the homologous Mn and Fe superoxide dismutases have the same arrangement of alpha-helices, and their active sites contain the same type and arrangement of amino acid side-chains. They are usually dimers, but occasionally tetramers, manganese – Nearly all mitochondria, and many bacteria, contain a form with manganese, For example, the Mn-SOD found in human mitochondria. The ligands of the ions are 3 histidine side-chains, an aspartate side-chain. This has a structure built from right-handed 4-helix bundles, each containing N-terminal hooks that chelate a Ni ion. The Ni-hook contains the motif His-Cys-X-X-Pro-Cys-Gly-X-Tyr, it provides most of the interactions critical for binding and catalysis and is, therefore
15.
SOD1
–
Superoxide dismutase also known as superoxide dismutase 1 or SOD1 is an enzyme that in humans is encoded by the SOD1 gene, located on chromosome 21. SOD1 is one of three superoxide dismutases. It is implicated in apoptosis and amyotrophic lateral sclerosis, SOD1 is a 32 kDa homodimer which forms a β-barrel and contains an intramolecular disulfide bond and a binuclear Cu/Zn site in each subunit. This Cu/Zn site holds the copper and an ion and is responsible for catalyzing the disproportionation of superoxide to hydrogen peroxide. The copper chaperone for Sod1 facilitates copper insertion and disulfide oxidation, though SOD1 is synthesized in the cytosol can mature there, the fraction of expressed, and still immature, SOD1 targeted to the mitochondria must be inserted into the intermembrane space. There, it forms the disulfide bond, though not metallation, the mature protein is highly stable, but unstable when in its metal-free and disulfide-reduced forms. This manifests in vitro, as the loss of metal results in increased SOD1 aggregation, and in disease models. Moreover, the surface-exposed reduced cysteines could participate in disulfide crosslinking and, thus, SOD1 binds copper and zinc ions and is one of three superoxide dismutases responsible for destroying free superoxide radicals in the body. Hydrogen peroxide can then be broken down by another enzyme called catalase, SOD1 has been postulated to localize to the outer mitochondrial membrane, where superoxide anions would be generated, or the intermembrane space. The exact mechanisms for its localization remains unknown, but its aggregation to the OMM has been attributed to its association with BCL-2, two models suggest SOD1 inhibits apoptosis by interacting with BCL-2 proteins or the mitochondria itself. The SOD1 enzyme is an important constituent in apoptotic signaling and oxidative stress, most notably as part of the death pathway. Programmed cell death is a genetic and biochemical pathway essential to metazoans. An intact death pathway is required for embryonic development and the maintenance of normal tissue homeostasis. Apoptosis has proven to be interwoven with other essential cell pathways. This is followed by fragmentation into apoptotic bodies that are removed by phagocytes. It is a mode of cell death defined by morphological, biochemical. It was first described as a shrinkage necrosis, and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear, the ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration
16.
SOD2
–
Superoxide dismutase 2, mitochondrial, also known as manganese-dependent superoxide dismutase, is an enzyme which in humans is encoded by the SOD2 gene on chromosome 6. A related pseudogene has been identified on chromosome 1, alternative splicing of this gene results in multiple transcript variants. This gene is a member of the superoxide dismutase family. It encodes a protein that forms a homotetramer and binds one manganese ion per subunit. This protein binds to the byproducts of oxidative phosphorylation and converts them to hydrogen peroxide. Mutations in this gene have been associated with cardiomyopathy, premature aging, sporadic motor neuron disease. The proximal promoter region contains multiple binding sites for transcription factors, including specific-1, activator protein 2 and this gene is a mitochondrial member of the iron/manganese superoxide dismutase family. It encodes a mitochondrial protein that forms a homotetramer and binds one manganese ion per subunit. The manganese site forms a trigonal bipyramidal geometry with four ligands from the protein and this solvent ligand is a hydroxide believed to serve as the electron acceptor of the enzyme. The active site cavity consists of a network of side chains of several residues associated by hydrogen bonding, extending from the ligand of the metal. Of note, the highly conserved residue Tyr34 plays a key role in the hydrogen-bonding network, alternate transcriptional splice variants, encoding different isoforms, have been characterized. This function allows SOD2 to clear mitochondrial reactive oxygen species and, as a result, as a result, this protein plays an antiapoptotic role against oxidative stress, ionizing radiation, and inflammatory cytokines. The SOD2 enzyme is an important constituent in apoptotic signaling and oxidative stress, most notably as part of the death pathway. Programmed cell death is a genetic and biochemical pathway essential to metazoans. An intact death pathway is required for embryonic development and the maintenance of normal tissue homeostasis. Apoptosis has proven to be interwoven with other essential cell pathways. This is followed by fragmentation into apoptotic bodies that are removed by phagocytes. It is a mode of cell death defined by morphological, biochemical
17.
SOD3
–
Extracellular superoxide dismutase is an enzyme that in humans is encoded by the SOD3 gene. This gene encodes a member of the superoxide dismutase protein family, sODs are antioxidant enzymes that catalyze the dismutation of two superoxide radicals into hydrogen peroxide and oxygen. The product of this gene is thought to protect the brain, lungs, a fraction of the protein is cleaved near the C-terminus before secretion to generate circulating tetramers that do not interact with the ECM
18.
Metal
–
A metal is a material that is typically hard, opaque, shiny, and has good electrical and thermal conductivity. Metals are generally malleable—that is, they can be hammered or pressed permanently out of shape without breaking or cracking—as well as fusible and ductile, about 91 of the 118 elements in the periodic table are metals, the others are nonmetals or metalloids. Some elements appear in both metallic and non-metallic forms, astrophysicists use the term metal to collectively describe all elements other than hydrogen and helium, the simplest two, in a star. The star fuses smaller atoms, mostly hydrogen and helium, to larger ones over its lifetime. In that sense, the metallicity of an object is the proportion of its matter made up of all chemical elements. Many elements and compounds that are not normally classified as metals become metallic under high pressures, the atoms of metallic substances are typically arranged in one of three common crystal structures, namely body-centered cubic, face-centered cubic, and hexagonal close-packed. In bcc, each atom is positioned at the center of a cube of eight others, in fcc and hcp, each atom is surrounded by twelve others, but the stacking of the layers differs. Some metals adopt different structures depending on the temperature, atoms of metals readily lose their outer shell electrons, resulting in a free flowing cloud of electrons within their otherwise solid arrangement. This provides the ability of metallic substances to easily transmit heat, while this flow of electrons occurs, the solid characteristic of the metal is produced by electrostatic interactions between each atom and the electron cloud. This type of bond is called a metallic bond, Metals are usually inclined to form cations through electron loss, reacting with oxygen in the air to form oxides over various timescales. Examples,4 Na + O2 →2 Na2O2 Ca + O2 →2 CaO4 Al +3 O2 →2 Al2O3, the transition metals are slower to oxidize because they form a passivating layer of oxide that protects the interior. Others, like palladium, platinum and gold, do not react with the atmosphere at all, some metals form a barrier layer of oxide on their surface which cannot be penetrated by further oxygen molecules and thus retain their shiny appearance and good conductivity for many decades. The oxides of metals are generally basic, as opposed to those of nonmetals, exceptions are largely oxides with very high oxidation states such as CrO3, Mn2O7, and OsO4, which have strictly acidic reactions. Painting, anodizing or plating metals are good ways to prevent their corrosion, however, a more reactive metal in the electrochemical series must be chosen for coating, especially when chipping of the coating is expected. Water and the two form an electrochemical cell, and if the coating is less reactive than the coatee. Metals in general have high conductivity, high thermal conductivity. Typically they are malleable and ductile, deforming under stress without cleaving, in terms of optical properties, metals are shiny and lustrous. Sheets of metal beyond a few micrometres in thickness appear opaque, although most metals have higher densities than most nonmetals, there is wide variation in their densities, lithium being the least dense solid element and osmium the densest
19.
Ceruloplasmin
–
Ceruloplasmin is a ferroxidase enzyme that in humans is encoded by the CP gene. Ceruloplasmin is the major copper-carrying protein in the blood, and in plays an role in iron metabolism. It was first described in 1948, another protein, hephaestin, is noted for its homology to ceruloplasmin, and also participates in iron and probably copper metabolism. Ceruloplasmin is an enzyme synthesized in the liver containing 6 atoms of copper in its structure, Ceruloplasmin carries more than 95% of the total copper in healthy human plasma. The rest is accounted for by macroglobulins, the molecular weight of human ceruloplasmin is reported to be 151kDa. A cis-regulatory element called the GAIT element is involved in the selective translational silencing of the Ceruloplasmin transcript, the silencing requires binding of a cytosolic inhibitor complex called IFN-gamma-activated inhibitor of translation to the GAIT element. Like any other protein, levels drop in patients with hepatic disease due to reduced synthesizing capabilities. However, the apoenzyme without copper is unstable, mutations in the ceruloplasmin gene, which are very rare, can lead to the genetic disease aceruloplasminemia, characterized by hyperferritinemia with iron overload. In the brain, this iron overload may lead to characteristic signs and symptoms, such as cerebellar ataxia, progressive dementia. Excess iron may also deposit in the liver, pancreas, and retina, leading to cirrhosis, endocrine abnormalities, and loss of vision, respectively
20.
Xanthine oxidase
–
Xanthine oxidase is a form of xanthine oxidoreductase, a type of enzyme that generates reactive oxygen species. These enzymes catalyze the oxidation of hypoxanthine to xanthine and can catalyze the oxidation of xanthine to uric acid. These enzymes play an important role in the catabolism of purines in some species, Xanthine oxidase is defined as an enzyme activity. The same protein, which in humans has the HGNC approved gene symbol XDH, for example, it efficiently converts 1-methylxanthine to 1-methyluric acid, but has little activity on 3-methylxanthine. Under some circumstances it can produce superoxide ion RH + H2O +2 O2 ⇌ ROH +2 O2− +2 H+. Because XO is an enzyme, with general low specificity, it can be combined with other compounds and enzymes and create reactive oxidants. XO has also found to produce the strong one-electron oxidant carbonate radical anion from oxidation with acetaldehyde in the presence of catalase. It was suggested that the radical was likely produced in one of the enzymes redox centers with a peroxymonocarbonate intermediate. Here is a diagram highlighting the pathways catalyzed by xanthine oxidase, the protein is large, having a molecular weight of 270 kDa, and has 2 flavin molecules,2 molybdenum atoms, and 8 iron atoms bound per enzymatic unit. The molybdenum atoms are contained as molybdopterin cofactors and are the sites of the enzyme. The iron atoms are part of ferredoxin iron-sulfur clusters and participate in electron transfer reactions, the active site of XO is composed of a molybdopterin unit with the molybdenum atom also coordinated by terminal oxygen, sulfur atoms and a terminal hydroxide. In the reaction with xanthine to uric acid, an oxygen atom is transferred from molybdenum to xanthine. The reformation of the molybdenum center occurs by the addition of water. Like other known molybdenum-containing oxidoreductases, the oxygen atom introduced to the substrate by XO originates from water rather than from dioxygen, Xanthine oxidase is a superoxide-producing enzyme found normally in serum and the lungs, and its activity is increased during influenza A infection. During severe liver damage, xanthine oxidase is released into the blood, because xanthine oxidase is a metabolic pathway for uric acid formation, the xanthine oxidase inhibitor allopurinol is used in the treatment of gout. Since xanthine oxidase is involved in the metabolism of 6-mercaptopurine, caution should be taken before administering allopurinol and 6-mercaptopurine, or its prodrug azathioprine, in conjunction. Xanthinuria is a genetic disorder where the lack of xanthine oxidase leads to high concentration of xanthine in blood. There is no treatment, sufferers are advised by doctors to avoid foods high in purine
21.
Ribonucleotide reductase
–
Ribonucleotide reductase, also known as ribonucleoside diphosphate reductase, is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. Deoxyribonucleotides in turn are used in the synthesis of DNA, the reaction catalyzed by RNR is strictly conserved in all living organisms. Furthermore, RNR plays a role in regulating the total rate of DNA synthesis so that DNA to cell mass is maintained at a constant ratio during cell division. A somewhat unusual feature of the RNR enzyme is that it catalyzes a reaction proceeds via a free radical mechanism of action. The substrates for RNR are ADP, GDP, CDP and UDP. dTDP is synthesized by another enzyme from dTMP, the iron-dependent enzyme, ribonucleotide reductase, is essential for DNA synthesis. Class I RNR enzymes are constructed from large RNR1 and small RNR2 subunits which associate to form a heterodimeric tetramer. Since the enzyme catalyses the de novo synthesis of deoxyribonucleotides, precursors to DNA synthesis, in Pfam, the second domain has been interpreted as two separate domains, a shorter all-alpha N-terminal domain, and a longer barrel C-terminal domain. RNR2 contains an iron center and a stable tyrosyl radical. In E. coli, the radical is located at position 122 providing the stable radical for the Class I RNR2 subunits. In A. aegypti, this radical is located at position 184. The tyrosyl radical is deeply buried inside the protein in a hydrophobic environment, the structure of two μ-oxo-linked irons is dominated by ligands that serve as iron binding sites, four carboxylates and two histidines. Association occurs between the C-terminus of RNR2 and the C-terminus of RNR1, enzymatic activity is dependent on association of the RNR1 and RNR2 subunits. The active site consists of the active groups from the RNR1 as well as the diferric center. Other residues of RNR2, such as aspartate, tryptophan, and these residues help in the transfer of the radical electron from tyrosine of RNR2 to cysteine of RNR1. The electron transfer begins on RNR2 tyrosine and continues in RNR2 to tryptophan, electron transfer from RNR2 to RNR1 occurs via tyrosine and continues on through tyrosine to cysteine in the active site. Site-directed mutations of the RNR primary structure indicate that all residues cited above participate in the long distance transfer of the radical to the active site. The enzyme ribonucleotide reductase catalyzes the de novo synthesis of dNDPs, catalysis of ribonucleoside 5’-diphosphates involves a reduction at the 2’-carbon of ribose 5-phosphate to form the 2’-deoxy derivative-reduced 2’-deoxyribonucleoside 5’-diphosphates. This reduction is initiated with the generation of a free radical, following a single reduction, RNR requires electrons donated from the dithiol groups of the protein thioredoxin
22.
Nitrogenase
–
Nitrogenases are enzymes that are produced by certain bacteria, such as cyanobacteria. These enzymes are responsible for the reduction of nitrogen to ammonia, nitrogenases are the only family of enzymes known to catalyze this reaction, which is a key step in the process of nitrogen fixation. Nitrogen fixation is required for all forms of life, with nitrogen being essential for the biosynthesis of molecules that create plants, animals, the equilibrium formation of ammonia from molecular hydrogen and nitrogen has an overall negative enthalpy of reaction, the activation energy is very high. Nitrogenase acts as a catalyst, reducing this energy barrier such that the reaction can take place at ambient temperatures, the nitrogenase complex consists of two proteins, The homodimeric Fe protein, a reductase which has a high reducing power and is responsible for the supply of electrons. The heterotetrameric MoFe protein, a nitrogenase which uses the electrons provided to reduce N2 to NH3, the Fe protein is a dimer of identical subunits which contains one cluster and weighs approximately 60-64kDa. The function of the Fe protein is to transfer electrons from a reducing agent, the transfer of electrons requires an input of chemical energy which comes from the binding and hydrolysis of ATP. The hydrolysis of ATP also causes a change within the nitrogenase complex, bringing the Fe protein. The MoFe protein is a heterotetramer consisting of two α subunits and two β subunits, weighing approximately 240-250kDa. The MoFe protein also contains two clusters, known as P-clusters, located at the interface between the α and β subunits and two FeMo cofactors, within the α subunits. The core of the P-cluster takes the form of two linked by a central sulfur atom. Each P-cluster is covalently linked to the MoFe protein by six cysteine residues, each FeMo cofactor consists of two non-identical clusters, and, which are linked by three sulfide ions. Each FeMo cofactor is covalently linked to the α subunit of the protein by one cysteine residue, electrons from the Fe protein enter the MoFe protein at the P-clusters, which then transfer the electrons to the FeMo cofactors. Each FeMo cofactor then acts as a site for nitrogen fixation, nitrogenase is an enzyme responsible for catalyzing nitrogen fixation, which is the reduction of nitrogen to ammonia and a process vital to sustaining life on Earth. There are three types of nitrogenase found in various nitrogen-fixing bacteria, molybdenum nitrogenase, vanadium nitrogenase, molybdenum nitrogenase, which can be found in diazotrophs and legumes, is the nitrogenase that has been studied the most extensively and thus is the most well characterized. Figures 1-2 display the structure and key catalytic components of molybdenum nitrogenase extracted from Azotobacter vinelandii. Vanadium nitrogenase and iron-only nitrogenase can both be found in species of Azotobacter as an alternative nitrogenase. Equations 1 and 2 show the reactions of nitrogen fixation in molybdenum nitrogenase. Component I is a MoFe protein in molybdenum nitrogenase, a VFe protein in vanadium nitrogenase, Component II is a Fe protein that contains the Fe-S cluster, which transfers electrons to Component I
23.
Phosphorus
–
Phosphorus is a chemical element with symbol P and atomic number 15. As an element, phosphorus exists in two major forms—white phosphorus and red phosphorus—but because it is reactive, phosphorus is never found as a free element on Earth. At 0. 099%, phosphorus is the most abundant pnictogen in the Earths crust, with few exceptions, minerals containing phosphorus are in the maximally oxidised state as inorganic phosphate rocks. The glow of phosphorus itself originates from oxidation of the white phosphorus — a process now termed chemiluminescence, together with nitrogen, arsenic, antimony, and bismuth, phosphorus is classified as a pnictogen. Phosphates are a component of DNA, RNA, ATP, and the phospholipids, demonstrating the link between phosphorus and life, elemental phosphorus was first isolated from human urine, and bone ash was an important early phosphate source. Phosphate mines contain fossils, especially marine fossils, because phosphate is present in the deposits of animal remains. Low phosphate levels are an important limit to growth in aquatic systems. The vast majority of compounds produced are consumed as fertilisers. Phosphate is needed to replace the phosphorus that plants remove from the soil, other applications include the role of organophosphorus compounds in detergents, pesticides, and nerve agents. Phosphorus exists as several forms that exhibit different properties. The two most common allotropes are white phosphorus and red phosphorus, from the perspective of applications and chemical literature, the most important form of elemental phosphorus is white phosphorus, often abbreviated as WP. It is a soft and waxy solid consists of tetrahedral P4 molecules. This P4 tetrahedron is also present in liquid and gaseous phosphorus up to the temperature of 800 °C when it starts decomposing to P2 molecules, White phosphorus exists in two crystalline forms, α and β. At room temperature, the α-form is stable, which is common and it has cubic crystal structure and at 195.2 K, it transforms into β-form. These forms differ in terms of the orientations of the constituent P4 tetrahedra. White phosphorus is the least stable, the most reactive, the most volatile, the least dense, White phosphorus gradually changes to red phosphorus. This transformation is accelerated by light and heat, and samples of white phosphorus almost always some red phosphorus. For this reason, white phosphorus that is aged or otherwise impure is also called yellow phosphorus, when exposed to oxygen, white phosphorus glows in the dark with a very faint tinge of green and blue
24.
Arsenic
–
Arsenic is a chemical element with symbol As and atomic number 33. Arsenic occurs in minerals, usually in combination with sulfur and metals. It has various allotropes, but only the form is important to industry. The primary use of arsenic is in alloys of lead. Arsenic is a common dopant in semiconductor electronic devices. Arsenic and its compounds, especially the trioxide, are used in the production of pesticides, treated wood products, herbicides, a few species of bacteria are able to use arsenic compounds as respiratory metabolites. Trace quantities of arsenic are a dietary element in rats, hamsters, goats, chickens. However, arsenic poisoning occurs in multicellular life if quantities are larger than needed, Arsenic contamination of groundwater is a problem that affects millions of people across the world. The three most common allotropes are metallic gray, yellow, and black arsenic, with gray being the most common. Gray arsenic adopts a structure consisting of many interlocked, ruffled, six-membered rings. Because of weak bonding between the layers, gray arsenic is brittle and has a relatively low Mohs hardness of 3.5. Nearest and next-nearest neighbors form an octahedral complex, with the three atoms in the same double-layer being slightly closer than the three atoms in the next. This relatively close packing leads to a density of 5.73 g/cm3. Gray arsenic is a semimetal, but becomes a semiconductor with a bandgap of 1. 2–1.4 eV if amorphized, gray arsenic is also the most stable form. Yellow arsenic is soft and waxy, and somewhat similar to tetraphosphorus, both have four atoms arranged in a tetrahedral structure in which each atom is bound to each of the other three atoms by a single bond. This unstable allotrope, being molecular, is the most volatile, least dense, solid yellow arsenic is produced by rapid cooling of arsenic vapor, As 4. It is rapidly transformed into gray arsenic by light, the yellow form has a density of 1.97 g/cm3. Black arsenic is similar in structure to red phosphorus, black arsenic can also be formed by cooling vapor at around 100–220 °C
25.
Glutaredoxin
–
Glutaredoxins are small redox enzymes of approximately one hundred amino-acid residues that use glutathione as a cofactor. Glutaredoxins are oxidized by substrates, and reduced non-enzymatically by glutathione, in contrast to thioredoxins, which are reduced by thioredoxin reductase, no oxidoreductase exists that specifically reduces glutaredoxins. Instead, glutaredoxins are reduced by the oxidation of glutathione, oxidized glutathione is then regenerated by glutathione reductase. Together these components compose the glutathione system, like thioredoxin, which functions in a similar way, glutaredoxin possesses an active centre disulfide bond. It exists in either a reduced or a form where the two cysteine residues are linked in an intramolecular disulfide bond. Glutaredoxins function as carriers in the glutathione-dependent synthesis of deoxyribonucleotides by the enzyme ribonucleotide reductase. Moreover, GRX act in antioxidant defence by reducing dehydroascorbate, peroxiredoxins, beside their function in antioxidant defence, bacterial and plant GRX were shown to bind iron-sulfur clusters and to deliver the cluster to enzymes on demand. Glutaredoxin has been sequenced in a variety of species, on the basis of extensive sequence similarity, it has been proposed that Vaccinia virus protein O2L is, it seems, a glutaredoxin. Bacteriophage T4 thioredoxin seems to be evolution-related, in position 5 of the pattern T4, thioredoxin has Val instead of Pro. Approximately 30 GRX isoforms are described in the model plant Arabidopsis thaliana and 48 in Oryza sativa L, according to their redox-active centre, they are subgrouped in six classes of the CSY-, CGFS-, CC-type and 3 groups with additional domain of unknown function. The CC-type GRXs are only found in higher plants, in Arabidopsis GRXs are involved in flower development and Salicylic acid signalling. Glutaredoxin subgroup InterPro, IPR014025 GLRX, GLRX2, GLRX3, GLRX5, PTGES2 Enzyme database entry Glutaredoxins at the US National Library of Medicine Medical Subject Headings
26.
GLRX2
–
Glutaredoxin 2 is an enzyme that in humans encoded by the GLRX2 gene. GLRX2, also known as GRX2, is a glutaredoxin family protein and this gene consists of four exons and three introns, spanned 10 kilobase pairs, and localized to chromosome 1q31. 2–31.3. Alternative splicing of GLRX2 leads to three isoforms of Grx2, one isoform, Grx2a, localizes to the mitochondria, is ubiquitously expressed in tissues, regulates mitochondrial redox homeostasis, and protects cells against oxidative stress. The transcripts of mitochondrial and nuclear Grx2 isoforms, Grx2a and Grx2b, respectively, differ in the first exon, grx2c is derived from alternative splicing of the Grx2b transcript with a shorter exon 1 than that of Grx2b. As a GRX family protein, Grx2 has an N-terminal thioredoxin domain and this amino acid substitution allows the main chain of Grx2 to be more flexible, promoting coordination of the iron-sulfur cluster and facilitating deglutathionylation by enhanced glutathione-binding. The cysteine pair falls outside of the site, and it is completely conserved in Grx2 proteins. A disulfide bond between this cysteine pair increases structural stability and provides resistance to over-oxidation induced enzymatic inactivation, Grx2 functions as a part of the cellular redox signaling pathway and antioxidant defense mechanism. As a GRX family protein, Grx2 acts as a donor to deglutathionylate proteins. It has also shown to reduce both thioredoxin 2 and thioredoxin 1 and protects cells from apoptosis induced by auranofin and 4-hydroxynonenal. Grx2 is also an electron acceptor and it can catalyze the reversible oxidation and glutathionylation of mitochondrial membrane thiol proteins. Additionally, NADPH and thioredoxin reductase efficiently reduce both the active site disulfide of Grx2 and the GSH-Grx2 intermediate formed in the reduction of glutathionylated substrates, enzymatic activity of Grx2 leads to its role in regulating redox-induced apoptosis. Grx2 over-expression protects cells against H2O2-induced damage while Grx2 knockdown showed the opposite effect, the protection role of Grx2 against H2O2-induced apoptosis is likely associated with its ability to preserve the electron transport chain complex I. In addition to H2O2, Grx2a overexpression is resistant to apoptosis induced by oxidative stress reagents, due to reduced cardiolipin oxidation. Interesting, Grx2 has also found to prevent aggregation of mutant SOD1 in mitochondria. Being a redox sensor, Grx2 activity is regulated by the oxidative state of the environment via iron-sulfur cluster. In steady state, Grx2 forms dimers to coordinate iron-sulfur clusters, during oxidative stress, the dimers separate into iron-free active monomers, which restore Grx2’s activity. In tumor cells, cells with decreased Grx2 are dramatically sensitized to cell death induced by the anti-cancer drug, in cardiovascular disease, Grx2a overexpression protects mouse heart from Dox and ischemia-induced cardiac injury, potentially via increasing mitochondrial protein glutathionylation. Conversely, Grx2 knockout hearts developed left ventricular hypertrophy and fibrosis, the mechanistic study shows that Grx2 knockout decreased mitochondrial ATP production, possibly via increased glutathionylation and thereby inhibition of complex I
27.
Isopenicillin N synthase
–
Isopenicillin N synthase is a non-heme iron-dependent enzyme belonging to the oxidoreductase family. This enzyme catalyzes the formation of isopenicillin N from δ--L-cysteinyl-D-valine, N--L-cysteinyl-D-valine + O2 ⇌ isopenicillin N +2 H2O This reaction is a key step in the biosynthesis of penicillin and cephalosporin antibiotics. The active sites of most isopenicillin N synthases contain an iron ion and this enzyme is also called isopenicillin N synthetase. Just two histidine residues and one aspartic acid residue are entirely conserved, therefore, it is highly significant that these two histidine residues, His214 and His270, and one aspartic acid residue, Asp216, are precisely the ones essential for activity. When ACV binds the active site, Gln330 and one water molecule are replaced by the ACV thiolate, the linear tripeptide δ--L-cysteinyl-D-valine must first be assembled from its component amino acids by N--L-cysteinyl-D-valine synthase. This allows for the binding of the substrate ACV to the thiol group of the cysteine residue. This ligation of the thiolate to the iron center anchors the ACV within the active site, the ligation of ACV results in a reduction of the FeI/FeII redox potential. This allows dioxygen to bind, which changes the oxidation state, an intramolecular hydrogen transfer takes place from C-3 of the cysteine residue, taking the iron back to the +II state. A thioaldehyde and a ligand are produced in this process. The hydroperoxy ligand deprotonates the amide which then closes the ring by a nucleophilic attack at the thioaldehyde carbon. This causes the hydrogen atom at the C-3 of the residue to come closer to the iron oxo ligand which is highly electrophilic. A second hydrogen transfer occurs, most likely producing an isopropyl radical which closes the ring by attacking the thiolate sulfur atom. This shows how IPNS occupies an early and key role in the pathway of all of the penicillins and cephalosporins. This class of antibiotics is the most widely used and they act by inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls, which is especially important in Gram-positive organisms. They will not work for infections caused by viruses, such as colds or the flu
. PMID 11752431.
