1.
Heme
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Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group, these are known as hemoproteins. Hemoproteins have diverse functions including the transportation of diatomic gases, chemical catalysis, diatomic gas detection. The heme iron serves as a source or sink of electrons during electron transfer or redox chemistry, in peroxidase reactions, the porphyrin molecule also serves as an electron source. In the transportation or detection of gases, the gas binds to the heme iron. During the detection of gases, the binding of the gas ligand to the heme iron induces conformational changes in the surrounding protein. Hemoproteins achieve their remarkable diversity by modifying the environment of the heme macrocycle within the protein matrix. For example, the ability of hemoglobin to effectively deliver oxygen to tissues is due to amino acid residues located near the heme molecule. Hemoglobin reversibly binds to oxygen in the lungs when the pH is high, when the situation is reversed, hemoglobin will release oxygen into the tissues. This phenomenon, which states that hemoglobins oxygen binding affinity is inversely proportional to both acidity and concentration of carbon dioxide, is known as the Bohr effect. There are several biologically important kinds of heme, The most common type is heme B, other important types include heme A, isolated hemes are commonly designated by capital letters while hemes bound to proteins are designated by lower case letters. Cytochrome a refers to the heme A in specific combination with membrane protein forming a portion of cytochrome c oxidase, the following carbon numbering system of porphyrins is an older numbering used by biochemists and not the 1–24 numbering system recommended by IUPAC which is shown in the table above. Heme l is the derivative of heme B which is attached to the protein of lactoperoxidase, eosinophil peroxidase. The addition of peroxide with the glutamyl-375 and aspartyl-225 of lactoperoxidase forms ester bonds between amino acid residues and the heme 1- and 5-methyl groups, respectively. Similar ester bonds with two methyl groups are thought to form in eosinophil and thyroid peroxidases. Heme l is one important characteristic of animal peroxidases, plant peroxidases incorporate heme B, lactoperoxidase and eosinophil peroxidase are protective enzymes responsible for the destruction of invading bacteria and virus. Thyroid peroxidase is the enzyme catalyzing the biosynthesis of the important thyroid hormones, because lactoperoxidase destroys invading organisms in the lungs and excrement, it is thought to be an important protective enzyme. Heme m is the derivative of heme B covalently bound at the site of myeloperoxidase. Heme m contains the two ester bonds at the heme 1- and 5-methyls as in heme l found in other mammalian peroxidases, myeloperoxidase is present in mammalian neutrophils and is responsible for the destruction of invading bacteria and viruse
2.
Protein
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Proteins are large biomolecules, or macromolecules, consisting of one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, a linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide, short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides, or sometimes oligopeptides. The individual amino acid residues are bonded together by peptide bonds, the sequence of amino acid residues in a protein is defined by the sequence of a gene, which is encoded in the genetic code. In general, the code specifies 20 standard amino acids, however. Sometimes proteins have non-peptide groups attached, which can be called prosthetic groups or cofactors, proteins can also work together to achieve a particular function, and they often associate to form stable protein complexes. Once formed, proteins only exist for a period of time and are then degraded and recycled by the cells machinery through the process of protein turnover. A proteins lifespan is measured in terms of its half-life and covers a wide range and they can exist for minutes or years with an average lifespan of 1–2 days in mammalian cells. Abnormal and or misfolded proteins are degraded more rapidly due to being targeted for destruction or due to being unstable. Like other biological macromolecules such as polysaccharides and nucleic acids, proteins are essential parts of organisms, many proteins are enzymes that catalyse biochemical reactions and are vital to metabolism. Proteins also have structural or mechanical functions, such as actin and myosin in muscle and the proteins in the cytoskeleton, other proteins are important in cell signaling, immune responses, cell adhesion, and the cell cycle. In animals, proteins are needed in the diet to provide the essential amino acids that cannot be synthesized, digestion breaks the proteins down for use in the metabolism. Methods commonly used to study structure and function include immunohistochemistry, site-directed mutagenesis, X-ray crystallography, nuclear magnetic resonance. Most proteins consist of linear polymers built from series of up to 20 different L-α-amino acids, all proteinogenic amino acids possess common structural features, including an α-carbon to which an amino group, a carboxyl group, and a variable side chain are bonded. Only proline differs from this structure as it contains an unusual ring to the N-end amine group. The amino acids in a chain are linked by peptide bonds. Once linked in the chain, an individual amino acid is called a residue, and the linked series of carbon, nitrogen. The peptide bond has two forms that contribute some double-bond character and inhibit rotation around its axis, so that the alpha carbons are roughly coplanar
3.
Ferrous
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Ferrous, in chemistry, indicates a divalent iron compound, as opposed to ferric, which indicates a trivalent iron compound. Outside chemistry, ferrous is a used to indicate the presence of iron. The word is derived from the Latin word ferrum, Ferrous metals include steel and pig iron and alloys of iron with other metals. Manipulation of atom-to-atom relationships between iron, carbon, and various alloying elements establishes the specific properties of ferrous metals, the term non-ferrous is used to indicate metals other than iron and alloys that do not contain an appreciable amount of iron. Ferromagnetism Steelmaking Ferrous metal recycling Iron oxide Ferrous chloride Iron bromide
4.
Ferric
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Ferric refers to iron-containing materials or compounds. In chemistry the term is reserved for iron with an number of +3. On the other hand, ferrous refers to iron with oxidation number of +2, iron is usually the most stable form of iron in air, as illustrated by the pervasiveness of rust, an insoluble iron-containing material. The word ferric is derived from the Latin word ferrum for iron, examples include iron-sulfur clusters, oxyhemoglobin, ferritin, and the cytochromes. The bioavailability of iron is of great interest because all forms of life require iron. Iron-deficiency anemia illustrates the problems resulting from low iron intake, many foods contain soluble iron compounds and are therefore necessary for good nutrition. The low bioavailability of iron affects all forms of life, bacteria secrete iron-attracting agents called siderophores that form soluble compounds of iron that can be reabsorbed into the cell and used in building iron-containing metalloproteins. The impact of increasing the bioavailability of iron was famously demonstrated by an experiment where an area of the ocean surface was sprayed with iron salts. After several days, the phytoplankton within the treated area bloomed to such an extent that the effect was visible from outer space and this fertilizing process has been proposed as a means to mitigate the carbon dioxide content of the atmosphere. Ferric iron mitigates the eutrophication of lakes by reducing the bioavailability of phosphorus in the water, mitigation arises because ferric phosphate is insoluble. Like iron, phosphate is often a limiting nutrient, and its reduction in concentration from solution limits the growth of algae, in water, ferric iron forms compounds that are often insoluble, at least near neutral pH. A salt of ferric iron hydrolyzes water and produces iron oxide-hydroxides while contributing hydrogen ions to the solution, in contrast, typical Na+ salts dissolve in water without lowering the pH. Aluminium behaves similarly to ferric ion, rust, a mixture of ferric hydroxide compounds, illustrates the low solubility of ferric ions in water. Various reagents cause rust to dissolve even at neutral pH and these ligands include EDTA, which forms a chelate complex with the ion, displacing the hydroxide and oxide ligands that comprise rust. For this reason, EDTA is often used to iron deposits or to deliver soluble iron in fertilizers. Citrate also solubilizes ferric ion at neutral pH, although its complexes are less stable than those of EDTA, Ferric iron is a d5 center, meaning that the metal has five valence electrons in the 3d orbital shell. The magnetism of ferric compounds is determined by these five electrons. Usually ferric ions are surrounded by six ligands arranged in octahedron, sometimes three and sometimes as many as seven ligands are observed
5.
Cytochrome c oxidase
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The enzyme cytochrome c oxidase or Complex IV, EC1.9.3.1 is a large transmembrane protein complex found in bacteria and the mitochondrion of eukaryotes. It is the last enzyme in the electron transport chain of mitochondria located in the mitochondrial membrane. It receives an electron from each of four cytochrome c molecules, the complex is a large integral membrane protein composed of several metal prosthetic sites and 14 protein subunits in mammals. In mammals, eleven subunits are nuclear in origin, and three are synthesized in the mitochondria, the complex contains two hemes, a cytochrome a and cytochrome a3, and two copper centers, the CuA and CuB centers. In fact, the cytochrome a3 and CuB form a center that is the site of oxygen reduction. The reduced CuA binuclear center now passes an electron on to cytochrome a, the two metal ions in this binuclear center are 4.5 Å apart and coordinate a hydroxide ion in the fully oxidized state. Crystallographic studies of cytochrome c oxidase show an unusual post-translational modification, linking C6 of Tyr and it plays a vital role in enabling the cytochrome a3- CuB binuclear center to accept four electrons in reducing molecular oxygen to water. The mechanism of reduction was formerly thought to involve a peroxide intermediate, however, the currently accepted mechanism involves a rapid four-electron reduction involving immediate oxygen-oxygen bond cleavage, avoiding any intermediate likely to form superoxide. COX subunits are encoded in both the nuclear and mitochondrial genomes, the three subunits that form the COX catalytic core are encoded in the mitochondrial genome. Hemes and cofactors are inserted into subunits I & II, subunits I and IV initiate assembly. Different subunits may associate to form intermediates that later bind to other subunits to form the COX complex. In post-assembly modifications, COX will form a homodimer, both dimers are connected by a cardiolipin molecule, which has been found to play a key role in stabilization of the holoenzyme complex. The dissociation of subunits VIIa and III in conjunction with the removal of cardiolipin results in loss of enzyme activity. Subunits encoded in the genome are known to play a role in enzyme dimerization. Mutations to these subunits eliminate COX function, assembly is known to occur in at least three distinct rate-determining steps. The products of these steps have been found, though specific subunit compositions have not been determined, synthesis and assembly of COX subunits I, II, and III are facilitated by translational activators, which interact with the 5’ untranslated regions of mitochondrial mRNA transcripts. Translational activators are encoded in the nucleus, the hydroxide ligand is protonated and lost as water, creating a void between the metals that is filled by O2. The oxygen is reduced, with two electrons coming from the Fe2+cytochrome a3, which is converted to the ferryl oxo form
6.
Cytochrome P450
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Cytochromes P450 are proteins of the superfamily containing heme as a cofactor and, therefore, are hemoproteins. CYPs use a variety of small and large molecules as substrates in enzymatic reactions and they are, in general, the terminal oxidase enzymes in electron transfer chains, broadly categorized as P450-containing systems. The term P450 is derived from the peak at the wavelength of the absorption maximum of the enzyme when it is in the reduced state. CYP enzymes have been identified in all kingdoms of life, animals, plants, fungi, protists, bacteria, archaea, however, they are not omnipresent, for example, they have not been found in Escherichia coli. More than 200,000 distinct CYP proteins are known, most CYPs require a protein partner to deliver one or more electrons to reduce the iron. Cytochrome b5 can also contribute reducing power to this system after being reduced by cytochrome b5 reductase, mitochondrial P450 systems, which employ adrenodoxin reductase and adrenodoxin to transfer electrons from NADPH to P450. Bacterial P450 systems, which employ a ferredoxin reductase and a ferredoxin to transfer electrons to P450, cYB5R/cyb5/P450 systems, in which both electrons required by the CYP come from cytochrome b5. FMN/Fd/P450 systems, originally found in Rhodococcus species, in which a FMN-domain-containing reductase is fused to the CYP, P450 only systems, which do not require external reducing power. Notable ones include thromboxane synthase, prostacyclin synthase, and CYP74A, the most common reaction catalyzed by cytochromes P450 is a monooxygenase reaction, e. g. The convention is to italicise the name referring to the gene. For example, CYP2E1 is the gene encodes the enzyme CYP2E1—one of the enzymes involved in paracetamol metabolism. The CYP nomenclature is the naming convention, although occasionally CYP450 or CYP450 is used synonymously. However, some gene or enzyme names for CYPs may differ from this nomenclature, denoting the catalytic activity, examples include CYP5A1, thromboxane A2 synthase, abbreviated to TBXAS1, and CYP51A1, lanosterol 14-α-demethylase, sometimes unofficially abbreviated to LDM according to its substrate and activity. The current nomenclature guidelines suggest that members of new CYP families share at least 40% amino acid identity, there are nomenclature committees that assign and track both base gene names and allele names. The active site of cytochrome P450 contains a heme-iron center, the iron is tethered to the protein via a cysteine thiolate ligand. This cysteine and several flanking residues are conserved in known CYPs and have the formal PROSITE signature consensus pattern - - x - - - - - C - -. Because of the vast variety of reactions catalyzed by CYPs, the activities and properties of the many CYPs differ in many aspects. In general, the P450 catalytic cycle proceeds as follows, Substrate binds in proximity to the heme group, Substrate binding induces electron transfer from NADH via cytochrome P450 reductase or another associated reductase
7.
David Keilin
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David Keilin FRS was an entomologist, among other things. He was born in Moscow in 1887 and his family returned to Warsaw early in his youth and he did not attend school until age ten due to ill health and asthma. Only seven years later, in 1904, he enrolled in the University of Liège and he later studied at Magdalene College, Cambridge, and became a British citizen. He made extensive contributions to entomology and parasitology during his career and he published thirty-nine papers between 1914 and 1923 on the reproduction of lice, the life-cycle of the horse bot-fly, the respiratory adaptations in fly larvae, and other subjects. He is most known for his research and rediscovery of cytochrome in the 1920s and it had been discovered by C. A. MacMunn in 1884, but that discovery had been forgotten or misunderstood. Keilin was elected a Fellow of the Royal Society in 1926 and he won its Royal Medal in 1939 and its Copley Medal in 1951
8.
Electron
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The electron is a subatomic particle, symbol e− or β−, with a negative elementary electric charge. Electrons belong to the first generation of the lepton particle family, the electron has a mass that is approximately 1/1836 that of the proton. Quantum mechanical properties of the include a intrinsic angular momentum of a half-integer value, expressed in units of the reduced Planck constant. As it is a fermion, no two electrons can occupy the same state, in accordance with the Pauli exclusion principle. Like all elementary particles, electrons exhibit properties of particles and waves, they can collide with other particles and can be diffracted like light. Since an electron has charge, it has an electric field. Electromagnetic fields produced from other sources will affect the motion of an electron according to the Lorentz force law, electrons radiate or absorb energy in the form of photons when they are accelerated. Laboratory instruments are capable of trapping individual electrons as well as electron plasma by the use of electromagnetic fields, special telescopes can detect electron plasma in outer space. Electrons are involved in applications such as electronics, welding, cathode ray tubes, electron microscopes, radiation therapy, lasers, gaseous ionization detectors. Interactions involving electrons with other particles are of interest in fields such as chemistry. The Coulomb force interaction between the positive protons within atomic nuclei and the negative electrons without, allows the composition of the two known as atoms, ionization or differences in the proportions of negative electrons versus positive nuclei changes the binding energy of an atomic system. The exchange or sharing of the electrons between two or more atoms is the cause of chemical bonding. In 1838, British natural philosopher Richard Laming first hypothesized the concept of a quantity of electric charge to explain the chemical properties of atoms. Irish physicist George Johnstone Stoney named this charge electron in 1891, electrons can also participate in nuclear reactions, such as nucleosynthesis in stars, where they are known as beta particles. Electrons can be created through beta decay of isotopes and in high-energy collisions. The antiparticle of the electron is called the positron, it is identical to the electron except that it carries electrical, when an electron collides with a positron, both particles can be totally annihilated, producing gamma ray photons. The ancient Greeks noticed that amber attracted small objects when rubbed with fur, along with lightning, this phenomenon is one of humanitys earliest recorded experiences with electricity. In his 1600 treatise De Magnete, the English scientist William Gilbert coined the New Latin term electricus, both electric and electricity are derived from the Latin ēlectrum, which came from the Greek word for amber, ἤλεκτρον
9.
Iron
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Iron is a chemical element with symbol Fe and atomic number 26. It is a metal in the first transition series and it is by mass the most common element on Earth, forming much of Earths outer and inner core. It is the fourth most common element in the Earths crust, like the other group 8 elements, ruthenium and osmium, iron exists in a wide range of oxidation states, −2 to +6, although +2 and +3 are the most common. Elemental iron occurs in meteoroids and other low oxygen environments, but is reactive to oxygen, fresh iron surfaces appear lustrous silvery-gray, but oxidize in normal air to give hydrated iron oxides, commonly known as rust. Unlike the metals that form passivating oxide layers, iron oxides occupy more volume than the metal and thus flake off, Iron metal has been used since ancient times, although copper alloys, which have lower melting temperatures, were used even earlier in human history. Pure iron is soft, but is unobtainable by smelting because it is significantly hardened and strengthened by impurities, in particular carbon. A certain proportion of carbon steel, which may be up to 1000 times harder than pure iron. Crude iron metal is produced in blast furnaces, where ore is reduced by coke to pig iron, further refinement with oxygen reduces the carbon content to the correct proportion to make steel. Steels and iron alloys formed with metals are by far the most common industrial metals because they have a great range of desirable properties. Iron chemical compounds have many uses, Iron oxide mixed with aluminium powder can be ignited to create a thermite reaction, used in welding and purifying ores. Iron forms binary compounds with the halogens and the chalcogens, among its organometallic compounds is ferrocene, the first sandwich compound discovered. Iron plays an important role in biology, forming complexes with oxygen in hemoglobin and myoglobin. Iron is also the metal at the site of many important redox enzymes dealing with cellular respiration and oxidation and reduction in plants. A human male of average height has about 4 grams of iron in his body and this iron is distributed throughout the body in hemoglobin, tissues, muscles, bone marrow, blood proteins, enzymes, ferritin, hemosiderin, and transport in plasma. The mechanical properties of iron and its alloys can be evaluated using a variety of tests, including the Brinell test, Rockwell test, the data on iron is so consistent that it is often used to calibrate measurements or to compare tests. An increase in the content will cause a significant increase in the hardness. Maximum hardness of 65 Rc is achieved with a 0. 6% carbon content, because of the softness of iron, it is much easier to work with than its heavier congeners ruthenium and osmium. Because of its significance for planetary cores, the properties of iron at high pressures and temperatures have also been studied extensively
