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NADPH Oxidase
NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white blood cells to engulf microorganisms. Human isoforms of the catalytic component of the complex include NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1, and DUOX2. Reaction NADPH oxidase catalyzes the production of a superoxide free radical by transferring one electron to oxygen from NADPH. : Types In mammals, NADPH oxidase is found in two types: one in white blood cells (neutrophilic) and the other in vascular cells, differing in biochemical structure and functions. Neutrophilic NADPH oxidase produces superoxide almost instantaneously, whereas the vascular enzyme produces superoxide in minutes to hours. Moreover, in white blood cells, superoxide has been found to transfer electrons across the membrane to extracellular oxygen, while in vascula ...
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NADPH
Nicotinamide adenine dinucleotide phosphate, abbreviated NADP or, in older notation, TPN (triphosphopyridine nucleotide), is a cofactor used in anabolic reactions, such as the Calvin cycle and lipid and nucleic acid syntheses, which require NADPH as a reducing agent ('hydrogen source'). It is used by all forms of cellular life. NADPH is the reduced form of NADP. NADP differs from NAD by the presence of an additional phosphate group on the 2' position of the ribose ring that carries the adenine moiety. This extra phosphate is added by NAD+ kinase and removed by NADP+ phosphatase. Biosynthesis NADP In general, NADP+ is synthesized before NADPH is. Such a reaction usually starts with NAD+ from either the de-novo or the salvage pathway, with NAD+ kinase adding the extra phosphate group. ADP-ribosyl cyclase allows for synthesis from nicotinamide in the salvage pathway, and NADP+ phosphatase can convert NADPH back to NADH to maintain a balance. Some forms of the NAD+ kinas ...
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Rho Family Of GTPases
The Rho family of GTPases is a family of small (~21 kDa) signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants. Three members of the family have been studied in detail: Cdc42, Rac1, and RhoA. All G proteins are "molecular switches", and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions. History Identification of the Rho family of GTPases began in the mid-1980s. The first identified Rho member was RhoA, isolated serendipitously in 1985 from a low stringency cDNA screening. Rac1 and Rac2 were identified next, in 1989 followed by Cdc42 in 1990. Eight additional mammalian Rho members were identified from biological screenings until the late 1990s, a turning point in biology where availability of complete genome seq ...
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Respiratory Burst
Respiratory burst (or oxidative burst) is the rapid release of the reactive oxygen species (ROS), superoxide anion () and hydrogen peroxide (), from different cell types. This is usually utilised for mammalian immunological defence, but also plays a role in cell signalling. Respiratory burst is also implicated in the ovum of animals following fertilization. It may also occur in plant cells. Immunity Immune cells can be divided into myeloid cells and lymphoid cells. Myeloid cells, including macrophages and neutrophils, are especially implicated in the respiratory burst. They are phagocytic, and the respiratory burst is vital for the subsequent degradation of internalised bacteria or other pathogens. This is an important aspect of the innate immunity. Respiratory burst requires a 10 to 20 fold increase in oxygen consumption through NADPH oxidase ( NOX2 in humans) activity. NADPH is the key substrate of NOX2, and bears reducing power. Glycogen breakdown is vital to produce NAD ...
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Reactive Oxygen Species
In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () produces superoxide (), which is the precursor to most other reactive oxygen species: :O2 + e^- -> \ ^\bullet O2- Dismutation of superoxide produces hydrogen peroxide (): :2 H+ + \ ^\bullet O2^- + \ ^\bullet O2^- -> H2O2 + O2 Hydrogen peroxide in turn may be partially reduced, thus forming hydroxide ions and hydroxyl radicals (), or fully reduced to water: :H2O2 + e^- -> HO^- + \ ^\bullet OH :2 H+ + 2 e- + H2O2 -> 2 H2O In a biological context, ROS are byproducts of the normal metabolism of oxygen. ROS have roles in cell signaling and homeostasis. ROS are intrinsic to cellular functioning, and are present at low and stationary levels in normal cells. In plants, ROS are involved in metabolic processes related to photoprotection and toleran ...
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Cytosolic
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into many compartments. In the eukaryotic cell, the cytosol is surrounded by the cell membrane and is part of the cytoplasm, which also comprises the mitochondria, plastids, and other organelles (but not their internal fluids and structures); the cell nucleus is separate. The cytosol is thus a liquid matrix around the organelles. In prokaryotes, most of the chemical reactions of metabolism take place in the cytosol, while a few take place in membranes or in the periplasmic space. In eukaryotes, while many metabolic pathways still occur in the cytosol, others take place within organelles. The cytosol is a complex mixture of substances dissolved in water. Although water forms the large majority of the cytosol, its structure and propertie ...
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Figure 2
Figure may refer to: General *A shape, drawing, depiction, or geometric configuration *Figure (wood), wood appearance *Figure (music), distinguished from musical motif *Noise figure, in telecommunication *Dance figure, an elementary dance pattern *A person's figure, human physical appearance Arts *Figurine, a miniature statuette representation of a creature *Action figure, a posable jointed solid plastic character figurine *Figure painting, realistic representation, especially of the human form *Figure drawing *Model figure, a scale model of a creature Writing *figure, in writing, a type of floating block (text, table, or graphic separate from the main text) *Figure of speech, also called a rhetorical figure *Christ figure, a type of character * in typesetting, text figures and lining figures Accounting *Figure, a synonym for number *Significant figures in a decimal number Science *Figure of the Earth, the size and shape of the Earth in geodesy Sports *Figure (horse), a st ...
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P67phox
Neutrophil cytosol factor 2 is a protein that in humans is encoded by the ''NCF2'' gene. Function This gene encodes neutrophil cytosolic factor 2, the 67-kilodalton cytosolic subunit of the multi-protein complex known as NADPH oxidase found in neutrophils. This oxidase produces a burst of superoxide which is delivered to the lumen of the neutrophil phagosome. Mutations in this gene, as well as in other NADPH oxidase subunits, can result in chronic granulomatous disease Chronic granulomatous disease (CGD), also known as Bridges–Good syndrome, chronic granulomatous disorder, and Quie syndrome, is a diverse group of hereditary diseases in which certain cells of the immune system have difficulty forming the reacti .... References Further reading * * * * * * * * * * * * * * * * * External links

* {{gene-1-stub ...
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P47phox
Neutrophil cytosol factor 1, also known as p47phox, is a protein that in humans is encoded by the ''NCF1'' gene. Function The protein encoded by this gene is a 47 kDa cytosolic subunit of neutrophil NADPH oxidase. This oxidase is a multicomponent enzyme that is activated to produce superoxide anion. Mutations in this gene have been associated with chronic granulomatous disease. Genetic variability in the NCF1 gene has been found to be related to a higher chance of getting autoimmune diseases such as Sjögren's syndrome, rheumatoid arthritis and lupus erythematosus. p47 is vital to the activation of NADPH oxidase. P47 becomes heavily phosphorylated Interactions Neutrophil cytosolic factor 1 has been shown to interact with: * Moesin, * Neutrophil cytosolic factor 4, and * RELA Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the ''RELA'' gene. RELA, also known as p65, is a REL-associated protein inv ...
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P40phox
Neutrophil cytosol factor 4 is a protein that in humans is encoded by the ''NCF4'' gene. Function The protein encoded by this gene is a cytosolic regulatory component of the superoxide-producing phagocyte NADPH-oxidase, a multicomponent enzyme system important for host defense. This protein is preferentially expressed in cells of myeloid lineage. It interacts primarily with neutrophil cytosolic factor 2 (NCF2/p67-phox) to form a complex with neutrophil cytosolic factor 1 (NCF1/p47-phox), which further interacts with the small G protein RAC1 and translocates to the membrane upon cell stimulation. This complex then activates flavocytochrome b, the membrane-integrated catalytic core of the enzyme system. The PX domain of this protein can bind phospholipid products of the PI(3) kinase, which suggests its role in PI(3) kinase-mediated signaling events. The phosphorylation of this protein was found to negatively regulate the enzyme activity. Alternatively spliced transcript variants en ...
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P22phox
p22phox Protein, also known as the human neutrophil cytochrome b light chain (CYBA), is an essential component of the membrane-associated enzyme phagocyte NADPH-oxidaseDinauer MC, Pierce EA, Bruns GA, Curnutte JT, Orkin SH. "Human neutrophil cytochrome b light chain (p22-phox). Gene structure, chromosomal location, and mutations in cytochrome-negative autosomal recessive chronic granulomatous disease." ''J Clin Invest.'' November 1990; 86(5): 1729-37. This enzyme uses NADH or NADPH as the electron donor for the one electron reduction of oxygen to produce superoxide anion, a reactive oxygen species (ROS),Xu Q, Yuan F, Wu J. "Polymorphisms of C242T and A640G in CYBA Gene and the risk of coronary artery disease: A meta-analysis." ''PLoS One''. 2014; 9(1): e84251 and a functionally important step for the antimicrobial activity of phagocytic cells. p22phox is also expressed in many other human cells such as endothelial and vascular smooth muscle cells, including those within the co ...
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Gp91-PHOX
NADPH oxidase 2 (Nox2), also known as cytochrome b(558) subunit beta or Cytochrome b-245 heavy chain, is a protein that in humans is encoded by the ''NOX2'' gene (also called ''CYBB'' gene). The protein is a superoxide generating enzyme which forms reactive oxygen species (ROS). Function The ''CYBB ''gene encode cytochrome b-245, beta chain. This protein is subunit of a group of proteins that forms an enzyme complex called NADPH oxidase, which plays an essential role in the immune system. Within this complex, the cytochrome b-245, beta chain has an alpha chain partner (produced from the ''CYBA'' gene). Both alpha and beta chains are required for either to function and the NADPH oxidase complex requires both chains in order to be functional. It has been proposed as a primary component of the microbicidal oxidase system of phagocytes. Nox2 is the catalytic, membrane-bound subunit of NADPH oxidase. It is inactive until it binds to the membrane-anchored p22''phox'', forming the ...
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Phagocytic
Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is called a phagocyte. In a multicellular organism's immune system, phagocytosis is a major mechanism used to remove pathogens and cell debris. The ingested material is then digested in the phagosome. Bacteria, dead tissue cells, and small mineral particles are all examples of objects that may be phagocytized. Some protozoa use phagocytosis as means to obtain nutrients. History Phagocytosis was first noted by Canadian physician William Osler (1876), and later studied and named by Élie Metchnikoff (1880, 1883). In immune system Phagocytosis is one main mechanisms of the innate immune defense. It is one of the first processes responding to infection, and is also one of the initiating branches of an adaptive immune response. Although mo ...
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