3BRT
53-459: 1147 12675 ENSG00000213341 ENSMUSG00000025199 O15111 Q60680 NM_001278 NM_001320928 NM_001162410 NM_007700 NP_001269 NP_001307857 n/a Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK-α) also known as IKK1 or conserved helix-loop-helix ubiquitous kinase (CHUK) is a protein kinase that in humans is encoded by the CHUK gene . IKK-α
106-426: A hydride ion . Reductants in chemistry are very diverse. Electropositive elemental metals , such as lithium , sodium , magnesium , iron , zinc , and aluminium , are good reducing agents. These metals donate electrons relatively readily. Hydride transfer reagents , such as NaBH 4 and LiAlH 4 , reduce by atom transfer: they transfer the equivalent of hydride or H . These reagents are widely used in
159-411: A gas. Later, scientists realized that the metal atom gains electrons in this process. The meaning of reduction then became generalized to include all processes involving a gain of electrons. Reducing equivalent refers to chemical species which transfer the equivalent of one electron in redox reactions. The term is common in biochemistry . A reducing equivalent can be an electron or a hydrogen atom as
212-459: A more easily corroded " sacrificial anode " to act as the anode . The sacrificial metal, instead of the protected metal, then corrodes. A common application of cathodic protection is in galvanized steel, in which a sacrificial zinc coating on steel parts protects them from rust. Oxidation is used in a wide variety of industries, such as in the production of cleaning products and oxidizing ammonia to produce nitric acid . Redox reactions are
265-574: A number of protein phosphatases, which remove the phosphate groups that are added to specific serine or threonine residues of the kinase and are required to maintain the kinase in an active conformation. Tyrosine -specific protein kinases ( EC 2.7.10.1 and EC 2.7.10.2 ) phosphorylate tyrosine amino acid residues, and like serine/threonine-specific kinases are used in signal transduction . They act primarily as growth factor receptors and in downstream signaling from growth factors. Some examples include: These kinases consist of extracellular domains,
318-465: A number of signaling cascades, in particular those involved in cytokine signaling (but also others, including growth hormone ). One such receptor-associated tyrosine kinase is Janus kinase (JAK), many of whose effects are mediated by STAT proteins . ( See JAK-STAT pathway . ) Some kinases have dual-specificity kinase activities. For example, MEK (MAPKK), which is involved in the MAP kinase cascade,
371-489: A protein kinase involves removing a phosphate group from ATP and covalently attaching it to one of three amino acids that have a free hydroxyl group . Most kinases act on both serine and threonine , others act on tyrosine , and a number ( dual-specificity kinases ) act on all three. There are also protein kinases that phosphorylate other amino acids, including histidine kinases that phosphorylate histidine residues. Eukaryotic protein kinases are enzymes that belong to
424-413: A redox reaction that takes place in a cell, the potential difference is: However, the potential of the reaction at the anode is sometimes expressed as an oxidation potential : The oxidation potential is a measure of the tendency of the reducing agent to be oxidized but does not represent the physical potential at an electrode. With this notation, the cell voltage equation is written with a plus sign In
477-646: A therapeutic option for the treatment of inflammatory diseases and cancer. Mutations in IKK-α in humans have been linked to lethal fetal malformations. The phenotype of these mutant fetuses is similar to the mouse IKK-α null phenotype, and is characterized by shiny, thickened skin and truncated limbs. Decreased IKK-α activity has been reported in a large percentage of human squamous cell carcinomas, and restoring IKK-α in mouse models of skin cancer has been shown to have an anti-tumorigenic effect. IKK-α has been shown to interact with: Protein kinase A protein kinase
530-454: A transmembrane spanning alpha helix , and an intracellular tyrosine kinase domain protruding into the cytoplasm . They play important roles in regulating cell division , cellular differentiation , and morphogenesis . More than 50 receptor tyrosine kinases are known in mammals. The extracellular domains serve as the ligand -binding part of the molecule, often inducing the domains to form homo- or heterodimers . The transmembrane element
583-541: A very extensive family of proteins that share a conserved catalytic core. The structures of over 280 human protein kinases have been determined. There are a number of conserved regions in the catalytic domain of protein kinases. In the N-terminal extremity of the catalytic domain there is a glycine -rich stretch of residues in the vicinity of a lysine amino acid, which has been shown to be involved in ATP binding. In
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#1732772572860636-408: A whole reaction. In electrochemical reactions the oxidation and reduction processes do occur simultaneously but are separated in space. Oxidation originally implied a reaction with oxygen to form an oxide. Later, the term was expanded to encompass substances that accomplished chemical reactions similar to those of oxygen. Ultimately, the meaning was generalized to include all processes involving
689-596: Is a kinase which selectively modifies other proteins by covalently adding phosphates to them ( phosphorylation ) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a functional change of the target protein ( substrate ) by changing enzyme activity , cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. There are two main types of protein kinase. The great majority are serine/threonine kinases , which phosphorylate
742-419: Is a both a serine/threonine and tyrosine kinase. Histidine kinases are structurally distinct from most other protein kinases and are found mostly in prokaryotes as part of two-component signal transduction mechanisms. A phosphate group from ATP is first added to a histidine residue within the kinase, and later transferred to an aspartate residue on a 'receiver domain' on a different protein, or sometimes on
795-417: Is a frequent cause of disease, in particular cancer, wherein kinases regulate many aspects that control cell growth, movement and death. Drugs that inhibit specific kinases are being developed to treat several diseases, and some are currently in clinical use, including Gleevec ( imatinib ) and Iressa ( gefitinib ). Drug developments for kinase inhibitors are started from kinase assays Archived 2014-11-26 at
848-432: Is a single α helix. The intracellular or cytoplasmic Protein kinase domain is responsible for the (highly conserved) kinase activity, as well as several regulatory functions. Ligand binding causes two reactions: Autophosphorylation stabilizes the active conformation of the kinase domain. When several amino acids suitable for phosphorylation are present in the kinase domain (e.g., the insulin-like growth factor receptor),
901-408: Is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a decrease in the oxidation state. The oxidation and reduction processes occur simultaneously in the chemical reaction. There are two classes of redox reactions: "Redox" is a portmanteau of
954-429: Is also called an electron acceptor . Oxidants are usually chemical substances with elements in high oxidation states (e.g., N 2 O 4 , MnO 4 , CrO 3 , Cr 2 O 7 , OsO 4 ), or else highly electronegative elements (e.g. O 2 , F 2 , Cl 2 , Br 2 , I 2 ) that can gain extra electrons by oxidizing another substance. Oxidizers are oxidants, but
1007-447: Is also known as its reduction potential ( E red ), or potential when the half-reaction takes place at a cathode. The reduction potential is a measure of the tendency of the oxidizing agent to be reduced. Its value is zero for H + e → 1 ⁄ 2 H 2 by definition, positive for oxidizing agents stronger than H (e.g., +2.866 V for F 2 ) and negative for oxidizing agents that are weaker than H (e.g., −0.763V for Zn ). For
1060-469: Is dependent on these ratios. Redox mechanisms also control some cellular processes. Redox proteins and their genes must be co-located for redox regulation according to the CoRR hypothesis for the function of DNA in mitochondria and chloroplasts . Wide varieties of aromatic compounds are enzymatically reduced to form free radicals that contain one more electron than their parent compounds. In general,
1113-432: Is mined as its magnetite (Fe 3 O 4 ). Titanium is mined as its dioxide, usually in the form of rutile (TiO 2 ). These oxides must be reduced to obtain the corresponding metals, often achieved by heating these oxides with carbon or carbon monoxide as reducing agents. Blast furnaces are the reactors where iron oxides and coke (a form of carbon) are combined to produce molten iron. The main chemical reaction producing
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#17327725728601166-505: Is not the reverse of the redox reaction in cellular respiration: Biological energy is frequently stored and released using redox reactions. Photosynthesis involves the reduction of carbon dioxide into sugars and the oxidation of water into molecular oxygen. The reverse reaction, respiration, oxidizes sugars to produce carbon dioxide and water. As intermediate steps, the reduced carbon compounds are used to reduce nicotinamide adenine dinucleotide (NAD ) to NADH, which then contributes to
1219-441: Is oxidized, and the oxidant or oxidizing agent gains electrons and is reduced. The pair of an oxidizing and reducing agent that is involved in a particular reaction is called a redox pair. A redox couple is a reducing species and its corresponding oxidizing form, e.g., Fe / Fe .The oxidation alone and the reduction alone are each called a half-reaction because two half-reactions always occur together to form
1272-608: Is part of the IκB kinase complex that plays an important role in regulating the NF-κB transcription factor. However, IKK-α has many additional cellular targets, and is thought to function independently of the NF-κB pathway to regulate epidermal differentiation . IKK-α is a member of the serine/threonine protein kinase family and forms a complex in the cell with IKK-β and NEMO . NF-κB transcription factors are normally held in an inactive state by
1325-456: The MAP kinases (acronym from: "mitogen-activated protein kinases"). Important subgroups are the kinases of the ERK subfamily, typically activated by mitogenic signals, and the stress-activated protein kinases JNK and p38. While MAP kinases are serine/threonine-specific, they are activated by combined phosphorylation on serine/threonine and tyrosine residues. Activity of MAP kinases is restricted by
1378-489: The Wayback Machine , the lead compounds are usually profiled for specificity before moving into further tests. Many profiling services are available from fluorescent-based assays to radioisotope based detections , and competition binding assays . Redox Redox ( / ˈ r ɛ d ɒ k s / RED -oks , / ˈ r iː d ɒ k s / REE -doks , reduction–oxidation or oxidation–reduction )
1431-417: The NF-κB pathway. In the mouse, IKK-α is required for cell cycle exit and differentiation of the embryonic keratinocytes . IKK-α null mice have a truncated snout and limbs, shiny skin, and die shortly after birth due to dehydration. Their epidermis retains a proliferative precursor cell population and lacks the outer two most differentiated cell layers. This function of IKK-α has been shown to be independent of
1484-476: The activity of the kinase can increase with the number of phosphorylated amino acids; in this case, the first phosphorylation switches the kinase from "off" to "standby". The active tyrosine kinase phosphorylates specific target proteins, which are often enzymes themselves. An important target is the ras protein signal-transduction chain. Tyrosine kinases recruited to a receptor following hormone binding are receptor-associated tyrosine kinases and are involved in
1537-573: The central part of the catalytic domain, there is a conserved aspartic acid , which is important for the catalytic activity of the enzyme. Serine/threonine protein kinases ( EC 2.7.11.1 ) phosphorylate the OH group of serine or threonine (which have similar side chains). Activity of these protein kinases can be regulated by specific events (e.g., DNA damage), as well as numerous chemical signals, including cAMP / cGMP , diacylglycerol , and Ca / calmodulin . One very important group of protein kinases are
1590-443: The copper sulfate solution, thus liberating free copper metal. The reaction is spontaneous and releases 213 kJ per 65 g of zinc. The ionic equation for this reaction is: As two half-reactions , it is seen that the zinc is oxidized: And the copper is reduced: A disproportionation reaction is one in which a single substance is both oxidized and reduced. For example, thiosulfate ion with sulfur in oxidation state +2 can react in
1643-479: The creation of a proton gradient , which drives the synthesis of adenosine triphosphate (ATP) and is maintained by the reduction of oxygen. In animal cells, mitochondria perform similar functions. Free radical reactions are redox reactions that occur as part of homeostasis and killing microorganisms . In these reactions, an electron detaches from a molecule and then re-attaches almost instantly. Free radicals are part of redox molecules and can become harmful to
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1696-476: The electron donor is any of a wide variety of flavoenzymes and their coenzymes . Once formed, these anion free radicals reduce molecular oxygen to superoxide and regenerate the unchanged parent compound. The net reaction is the oxidation of the flavoenzyme's coenzymes and the reduction of molecular oxygen to form superoxide. This catalytic behavior has been described as a futile cycle or redox cycling. Minerals are generally oxidized derivatives of metals. Iron
1749-415: The electrons cancel: The protons and fluoride combine to form hydrogen fluoride in a non-redox reaction: The overall reaction is: In this type of reaction, a metal atom in a compound or solution is replaced by an atom of another metal. For example, copper is deposited when zinc metal is placed in a copper(II) sulfate solution: In the above reaction, zinc metal displaces the copper(II) ion from
1802-446: The environment. Cellular respiration , for instance, is the oxidation of glucose (C 6 H 12 O 6 ) to CO 2 and the reduction of oxygen to water . The summary equation for cellular respiration is: The process of cellular respiration also depends heavily on the reduction of NAD to NADH and the reverse reaction (the oxidation of NADH to NAD ). Photosynthesis and cellular respiration are complementary, but photosynthesis
1855-660: The foundation of electrochemical cells, which can generate electrical energy or support electrosynthesis . Metal ores often contain metals in oxidized states, such as oxides or sulfides, from which the pure metals are extracted by smelting at high temperatures in the presence of a reducing agent. The process of electroplating uses redox reactions to coat objects with a thin layer of a material, as in chrome-plated automotive parts, silver plating cutlery , galvanization and gold-plated jewelry . Many essential biological processes involve redox reactions. Before some of these processes can begin, iron must be assimilated from
1908-413: The human body if they do not reattach to the redox molecule or an antioxidant . The term redox state is often used to describe the balance of GSH/GSSG , NAD /NADH and NADP /NADPH in a biological system such as a cell or organ . The redox state is reflected in the balance of several sets of metabolites (e.g., lactate and pyruvate , beta-hydroxybutyrate and acetoacetate ), whose interconversion
1961-415: The hydroxyl groups of serines and threonines in their targets. Most of the others are tyrosine kinases , although additional types exist. Protein kinases are also found in bacteria and plants . Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction . The chemical activity of
2014-516: The inhibitory proteins IκBs. IKK-α and IKK-β phosphorylate the IκB proteins, marking them for degradation via ubiquitination and allowing NF-κB transcription factors to go into the nucleus. Once activated, NF-κB transcription factors regulate genes that are implicated in many important cellular processes, including immune response, inflammation, cell death, and cell proliferation. IKK-α has been shown to function in epidermal differentiation independently of
2067-410: The kinase itself. The aspartyl phosphate residue is then active in signaling. Histidine kinases are found widely in prokaryotes, as well as in plants, fungi and eukaryotes. The pyruvate dehydrogenase family of kinases in animals is structurally related to histidine kinases, but instead phosphorylate serine residues, and probably do not use a phospho-histidine intermediate. Deregulated kinase activity
2120-413: The loss of electrons or the increase in the oxidation state of a chemical species. Substances that have the ability to oxidize other substances (cause them to lose electrons) are said to be oxidative or oxidizing, and are known as oxidizing agents , oxidants, or oxidizers. The oxidant removes electrons from another substance, and is thus itself reduced. Because it "accepts" electrons, the oxidizing agent
2173-492: The molten iron is: Electron transfer reactions are central to myriad processes and properties in soils, and redox potential , quantified as Eh (platinum electrode potential ( voltage ) relative to the standard hydrogen electrode) or pe (analogous to pH as -log electron activity), is a master variable, along with pH, that controls and is governed by chemical reactions and biological processes. Early theoretical research with applications to flooded soils and paddy rice production
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2226-666: The outermost cells in these embryos are hyperproliferative and fail to turn on critical epidermal genes. Different domains of the protein are required for this function of IKK-α in zebrafish than in mice, but in neither case does the NF-κB pathway seem to be implicated. IκB kinase α (IKKα) is a regulator of keratinocyte terminal differentiation and proliferation and plays a role in skin cancer. Activation of three major hydrogen peroxide-dependent pathways, EGF , FOXO1 , and IKK-α occur during injury-induced epidermal keratinocyte migration, adhesion, cytoprotection and wound healing. IKKα regulates human keratinocyte migration by surveillance of
2279-404: The presence of acid to form elemental sulfur (oxidation state 0) and sulfur dioxide (oxidation state +4). Thus one sulfur atom is reduced from +2 to 0, while the other is oxidized from +2 to +4. Cathodic protection is a technique used to control the corrosion of a metal surface by making it the cathode of an electrochemical cell . A simple method of protection connects protected metal to
2332-490: The protein's kinase activity and of the NF-κB pathway. Instead it is thought that IKK-α regulates skin differentiation by acting as a cofactor in the TGF-β / Smad2 / 3 signaling pathway. The zebrafish homolog of IKK-α has also been shown to play a role in the differentiation of the embryonic epithelium. Zebrafish embryos born from mothers that are mutant in IKK-α do not produce a differentiated outer epithelial monolayer. Instead,
2385-544: The reaction between hydrogen and fluorine , hydrogen is being oxidized and fluorine is being reduced: This spontaneous reaction releases 542 kJ per 2 g of hydrogen because the H-F bond is much stronger than the F-F bond. This reaction can be analyzed as two half-reactions . The oxidation reaction converts hydrogen to protons : The reduction reaction converts fluorine to the fluoride anion: The half-reactions are combined so that
2438-692: The redox environment after wounding. IKK-α is sulfenylated at a conserved cysteine residue in the kinase domain, which correlated with derepression of EGF promoter activity and increased EGF expression, indicating that IKK-α stimulates migration through dynamic interactions with the EGF promoter depending on the redox state within cells. IKK-α has also been reported to regulate the cell cycle protein cyclin D1 in an NF-κB-independent manner. Inhibition of IκB kinase (IKK) and IKK-related kinases, IKBKE (IKKε) and TANK-binding kinase 1 (TBK1), has been investigated as
2491-410: The reducing agent is also called an electron donor . Electron donors can also form charge transfer complexes with electron acceptors. The word reduction originally referred to the loss in weight upon heating a metallic ore such as a metal oxide to extract the metal. In other words, ore was "reduced" to metal. Antoine Lavoisier demonstrated that this loss of weight was due to the loss of oxygen as
2544-494: The reduction of carbonyl compounds to alcohols . A related method of reduction involves the use of hydrogen gas (H 2 ) as sources of H atoms. The electrochemist John Bockris proposed the words electronation and de-electronation to describe reduction and oxidation processes, respectively, when they occur at electrodes . These words are analogous to protonation and deprotonation . They have not been widely adopted by chemists worldwide, although IUPAC has recognized
2597-437: The term is mainly reserved for sources of oxygen, particularly in the context of explosions. Nitric acid is a strong oxidizer. Substances that have the ability to reduce other substances (cause them to gain electrons) are said to be reductive or reducing and are known as reducing agents , reductants, or reducers. The reductant transfers electrons to another substance and is thus itself oxidized. Because it donates electrons,
2650-658: The terms electronation and de-electronation. Redox reactions can occur slowly, as in the formation of rust , or rapidly, as in the case of burning fuel . Electron transfer reactions are generally fast, occurring within the time of mixing. The mechanisms of atom-transfer reactions are highly variable because many kinds of atoms can be transferred. Such reactions can also be quite complex, involving many steps. The mechanisms of electron-transfer reactions occur by two distinct pathways, inner sphere electron transfer and outer sphere electron transfer . Analysis of bond energies and ionization energies in water allows calculation of
2703-446: The thermodynamic aspects of redox reactions. Each half-reaction has a standard electrode potential ( E cell ), which is equal to the potential difference or voltage at equilibrium under standard conditions of an electrochemical cell in which the cathode reaction is the half-reaction considered, and the anode is a standard hydrogen electrode where hydrogen is oxidized: The electrode potential of each half-reaction
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#17327725728602756-448: The words "REDuction" and "OXidation." The term "redox" was first used in 1928. Oxidation is a process in which a substance loses electrons. Reduction is a process in which a substance gains electrons. The processes of oxidation and reduction occur simultaneously and cannot occur independently. In redox processes, the reductant transfers electrons to the oxidant. Thus, in the reaction, the reductant or reducing agent loses electrons and
2809-433: Was seminal for subsequent work on thermodynamic aspects of redox and plant root growth in soils. Later work built on this foundation, and expanded it for understanding redox reactions related to heavy metal oxidation state changes, pedogenesis and morphology, organic compound degradation and formation, free radical chemistry, wetland delineation, soil remediation , and various methodological approaches for characterizing
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