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Tenase
In coagulation, the coagulation factor X can be activated into factor Xa in two ways: either extrinsically or intrinsically. The activating complexes are together called tenase. Tenase is a blend word of "ten" and the suffix "-ase", which means, that the complex activates its substrate (inactive factor X) by cleaving it. Extrinsic tenase complex is made up of tissue factor, factor VII, and Ca2+ as an activating ion. Intrinsic tenase complex contains the active factor IX (IXa), its cofactor factor VIII (VIIIa), the substrate (factor X), and they are activated by negatively charged surfaces (such as glass, active platelet membrane, sometimes cell membrane of monocytes). These vitamin K-dependent procoagulant factors dock to this surface through their Gla domain Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain is a protein domain that contains post-translational modifications of many glutamate residues by vitamin K-dependent carboxylation to form γ-carboxygl ...
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Coagulation
Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a thrombus, blood clot. It results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. The process of coagulation involves Platelet-activating factor, activation, Cell adhesion, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin. Coagulation begins almost instantly after an injury to the endothelium that lines a blood vessel. Exposure of blood to the subendothelial space initiates two processes: changes in platelets, and the exposure of subendothelial Tissue factor, platelet tissue factor to coagulation factor VII, which ultimately leads to cross-linked fibrin formation. Platelets immediately form a plug at the site of injury; this is called ''primary hemostasis. Secondary hemostasis'' occurs simultaneously: additional coagulation factors beyond factor VII (#Coagulation factors, listed below) respond in a c ...
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Coagulation Factor X
Coagulation factor X (), or Stuart factor, is an enzyme of the coagulation cascade, encoded in humans by ''F10'' gene. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for its synthesis. Factor X is activated, by hydrolysis, into factor Xa by both factor IX with its cofactor, factor VIII in a complex known as intrinsic pathway; and factor VII with its cofactor, tissue factor in a complex known as extrinsic pathway. It is therefore the first member of the ''final common pathway'' or ''thrombin pathway''. It acts by cleaving prothrombin in two places (an Arg- Thr and then an Arg-Ile bond), which yields the active thrombin. This process is optimized when factor Xa is complexed with activated co-factor V in the prothrombinase complex. Factor Xa is inactivated by protein Z-dependent protease inhibitor (ZPI), a serine protease inhibitor (serpin). The affinity of this protein for factor Xa is increased 1000-f ...
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Factor Xa
Coagulation factor X (), or Stuart factor, is an enzyme of the coagulation cascade, encoded in humans by ''F10'' gene. It is a serine endopeptidase (protease group S1, PA clan). Factor X is synthesized in the liver and requires vitamin K for its synthesis. Factor X is activated, by hydrolysis, into factor Xa by both factor IX with its cofactor, factor VIII in a complex known as intrinsic pathway; and factor VII with its cofactor, tissue factor in a complex known as extrinsic pathway. It is therefore the first member of the ''final common pathway'' or ''thrombin pathway''. It acts by cleaving prothrombin in two places (an Arg- Thr and then an Arg- Ile bond), which yields the active thrombin. This process is optimized when factor Xa is complexed with activated co-factor V in the prothrombinase complex. Factor Xa is inactivated by protein Z-dependent protease inhibitor (ZPI), a serine protease inhibitor (serpin). The affinity of this protein for factor Xa is increa ...
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Platelet
Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no cell nucleus; they are fragments of cytoplasm from megakaryocytes which reside in bone marrow or Lung, lung tissue, and then enter the circulation. Platelets are found only in mammals, whereas in other vertebrates (e.g. birds, amphibians), thrombocytes circulate as intact agranulocyte, mononuclear cells. One major function of platelets is to contribute to hemostasis: the process of stopping bleeding at the site where the lining of vessels (endothelium) has been interrupted. Platelets gather at the site and, unless the interruption is physically too large, they plug the hole. First, platelets attach to substances outside the interrupted endothelium: ''adhesion (medicine), adhesion''. Second, they change shape, turn on receptors and secret ...
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Blend Word
In linguistics, a blend—also known as a blend word, lexical blend, or portmanteau—is a word formed by combining the meanings, and parts of the sounds, of two or more words together.Garner's Modern American Usage
p. 644.
English examples include '' smog'', coined by blending ''smoke'' and ''fog'', and '''', from ''motor'' ('' motorist'') and ''hotel''. A blend is similar to a
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Tissue Factor
Tissue factor, also called platelet tissue factor or Coagulation factor III, is a protein present in subendothelial tissue and leukocytes which plays a major role in coagulation and, in humans, is encoded by ''F3'' gene. Its role in the blood clotting is the initiation of thrombin formation from the zymogen prothrombin. Thromboplastin defines the cascade that leads to the activation of factor X—the tissue factor pathway. In doing so, it has replaced the previously named extrinsic pathway in order to eliminate ambiguity. Function The F3 gene encodes tissue factor also known as coagulation factor III, which is a cell surface glycoprotein. This factor enables cells to initiate the blood coagulation cascades, and it functions as the high-affinity receptor for the coagulation factor VII. The resulting complex provides a catalytic event that is responsible for initiation of the coagulation protease cascades by specific limited proteolysis. Unlike the other cofactors of these pr ...
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Factor VII
Coagulation factor VII (, formerly known as proconvertin) is a protein involved in coagulation and, in humans, is encoded by gene ''F7''. It is an enzyme of the serine protease class. Once bound to tissue factor released from damaged tissues, it is converted to factor VIIa (or ''blood-coagulation factor VIIa'', ''activated blood coagulation factor VII''), which in turn activates factor IX and factor X. Using genetic recombination a recombinant factor VIIa (eptacog alfa) (trade names include NovoSeven) has been approved by the FDA for the control of bleeding in hemophilia. It is sometimes used unlicensed in severe uncontrollable bleeding, although there have been safety concerns. A biosimilar form of recombinant activated factor VII (AryoSeven) is also available, but does not play any considerable role in the market. In April 2020, the US FDA approved a new rFVIIa product, eptacog beta (SEVENFACT), the first bypassing agent (BPA) approved in more than 2 decades. As an rFVIIa pr ...
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Ca2+
Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. Many enzymes require calcium ions as a cofactor, including several of the coagulation factors. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation. Plasma calcium levels in mammals are tightly regulated, electronic-book electronic- with bone acting as the major mineral storage site. Calcium ions, Ca2+, are released from bone into the bloodstream under controlled conditions. Calcium is transported through the bloodstream as dissolved ions or bound to proteins such as serum albumin. Parathyroid hormone secreted by the parathyroid gland regulates the resorption of Ca2+ from bone, reabsorption i ...
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Factor IX
Factor IX (), also known as Christmas factor, is one of the serine proteases involved in coagulation; it belongs to peptidase family S1. Deficiency of this protein causes haemophilia B. It was discovered in 1952 after a young boy named Stephen Christmas was found to be lacking this exact factor, leading to haemophilia. Coagulation factor IX is on the WHO Model List of Essential Medicines, World Health Organization's List of Essential Medicines. Physiology Factor IX is produced as a zymogen, an inactive precursor. It is processed to remove the signal peptide, Glycosylation, glycosylated and then cleaved by factor XIa (of the contact pathway) or factor VIIa (of the tissue factor pathway) to produce a two-chain form, where the chains are linked by a disulfide bridge. When activated into factor IXa, in the presence of Ca2+, membrane phospholipids, and a Factor VIII cofactor, it hydrolyses one arginine-isoleucine bond in factor X to form factor Xa. Factor IX is inhibited by ...
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Factor VIII
Coagulation factor VIII (Factor VIII, FVIII, also known as anti-hemophilic factor (AHF)) is an essential blood clotting protein. In humans, it is encoded by ''F8'' gene. Defects in this gene result in hemophilia A, an X-linked bleeding disorder. Factor VIII is produced in the liver's liver sinusoid, sinusoidal cells and endothelial cells outside the liver throughout the body. This protein circulates in the bloodstream in an inactive form, bound to another molecule called von Willebrand factor, until an injury that damages blood vessels occurs. In response to injury, coagulation factor VIII is activated and separates from von Willebrand factor. The active protein (sometimes written as coagulation factor VIIIa) interacts with another coagulation factor called factor IX. This interaction sets off a chain of additional chemical reactions that form a blood clot. Factor VIII participates in blood coagulation; it is a cofactor for factor IXa, which, in the presence of Ca2+ and phosph ...
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Cell Membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extracellular space). The cell membrane consists of a lipid bilayer, made up of two layers of phospholipids with cholesterols (a lipid component) interspersed between them, maintaining appropriate membrane fluidity at various temperatures. The membrane also contains membrane proteins, including integral proteins that span the membrane and serve as membrane transporters, and peripheral proteins that loosely attach to the outer (peripheral) side of the cell membrane, acting as enzymes to facilitate interaction with the cell's environment. Glycolipids embedded in the outer lipid layer serve a similar purpose. The cell membrane controls the movement of substances in and out of a cell, being selectively permeable to ions and organic mole ...
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Monocytes
Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and monocyte-derived dendritic cells. As a part of the vertebrate innate immune system monocytes also influence adaptive immune responses and exert tissue repair functions. There are at least three subclasses of monocytes in human blood based on their phenotypic receptors. Structure Monocytes are amoeboid in appearance, and have nongranulated cytoplasm. Thus they are classified as agranulocytes, although they might occasionally display some azurophil granules and/or vacuoles. With a diameter of 15–22 μm, monocytes are the largest cell type in peripheral blood. Monocytes are mononuclear cells and the ellipsoidal nucleus is often lobulated/indented, causing a bean-shaped or kidney-shaped appearance. Monocytes compose 2% to 10% of all leukocytes in the human body. Development Monocytes are produced by the bone marrow from precur ...
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