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Kinin Precursor
Kininogens are precursor proteins for kinins, biologically active polypeptides involved in blood coagulation, vasodilation, smooth muscle contraction, inflammatory regulation, and the regulation of the cardiovascular and renal systems. Types of kininogen There are two main types of kininogen (KNG), high-molecular-weight-kininogen and low-molecular-weight-kininogen, with a third type – T-kininogen – only found in rats but not humans. High molecular weight kininogen High-molecular-weight-kininogen (HK) is a non-enzymatic cofactor involved in the kinin-kallikrein system, which plays a role in blood coagulation, blood pressure regulation, and inflammation. It is synthesized in endothelial cells and is produced mostly by the liver. It is also a precursor protein for bradykinin. Low molecular weight kininogen Low-molecular-weight-kininogen (LK) is mainly a precursor protein for kallidin. LK, however, is not actively involved in blood coagulation, but its byproducts c ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Precursor
A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein (or peptide) that can be turned into an active form by post-translational modification, such as breaking off a piece of the molecule or adding on another molecule. The name of the precursor for a protein is often prefixed by ''pro-''. Examples include proinsulin and proopiomelanocortin, which are both prohormones. Protein precursors are often used by an organism when the subsequent protein is potentially harmful, but needs to be available on short notice and/or in large quantities. Enzyme precursors are called zymogens or proenzymes. Examples are enzymes of the digestive tract in humans. Some protein precursors are secreted from the cell. Many of these are synthesized with an N-terminal signal peptide that targets them for secretion. Like other proteins that contain a signal peptide, their name is prefixed by ''pre''. They are thus called pre-pro-proteins or pre-pro-peptides. The signal peptide i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Endothelial Cell
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel wall. Endothelial cells form the barrier between vessels and tissue and control the flow of substances and fluid into and out of a tissue. Endothelial cells in direct contact with blood are called vascular endothelial cells whereas those in direct contact with lymph are known as lymphatic endothelial cells. Vascular endothelial cells line the entire circulatory system, from the heart to the smallest capillaries. These cells have unique functions that include fluid filtration, such as in the glomerulus of the kidney, blood vessel tone, hemostasis, neutrophil recruitment, and hormone trafficking. Endothelium of the interior surfaces of the heart chambers is called endocardium. An impaired function can lead to serious health issues throug ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Bradykinin
Bradykinin (BK) (Greek brady-, slow; -kinin, kīn(eîn) to move) is a peptide that promotes inflammation. It causes arterioles to dilate (enlarge) via the release of prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor and makes veins constrict, via prostaglandin F2, thereby leading to leakage into capillary beds, due to the increased pressure in the capillaries. Bradykinin is a physiologically and pharmacologically active peptide of the kinin group of proteins, consisting of nine amino acids. A class of drugs called angiotensin converting enzyme inhibitors (ACE inhibitors) increase bradykinin levels by inhibiting its degradation, thereby increasing its blood pressure lowering effect. ACE inhibitors are FDA approved for the treatment of hypertension and heart failure. Structure Bradykinin, sometimes referred to as BK, is a 9-amino acid peptide chain. The amino acid sequence of bradykinin is: Arg-Pro-Pro-Gly- Phe-Ser-Pro- Phe- Arg (RPPGFSPFR). Its empi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Thrombin
Thrombin (, ''fibrinogenase'', ''thrombase'', ''thrombofort'', ''topical'', ''thrombin-C'', ''tropostasin'', ''activated blood-coagulation factor II'', ''blood-coagulation factor IIa'', ''factor IIa'', ''E thrombin'', ''beta-thrombin'', ''gamma-thrombin'') is a serine protease, an enzyme that, in humans, is encoded by the ''F2'' gene. Prothrombin (coagulation factor II) is proteolytically cleaved to form thrombin in the clotting process. Thrombin in turn acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin, as well as catalyzing many other coagulation-related reactions. History After the description of fibrinogen and fibrin, Alexander Schmidt hypothesised the existence of an enzyme that converts fibrinogen into fibrin in 1872. Prothrombin was discovered by Pekelharing in 1894. Physiology Synthesis Thrombin is produced by the enzymatic cleavage of two sites on prothrombin by activated Factor X (Xa). The activity of factor Xa is greatly ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Factor X
Factor X, also known by the eponym Stuart–Prower factor, is an enzyme () of the coagulation cascade. 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 tenase'') and factor VII with its cofactor, tissue factor (a complex known as ''extrinsic tenase''). 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-fold by the pr ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tissue Factor
Tissue factor, also called platelet tissue factor, factor III, or CD142, is a protein encoded by the ''F3'' gene, present in subendothelial tissue and leukocytes. Its role in the clotting process 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 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 protease cascades, which circulate as nonfunctional precursors, this factor is a potent ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks bonds. Proteases are involved in many biological functions, including digestion of ingested proteins, protein catabolism (breakdown of old proteins), and cell signaling. In the absence of functional accelerants, proteolysis would be very slow, taking hundreds of years. Proteases can be found in all forms of life and viruses. They have independently evolved multiple times, and different classes of protease can perform the same reaction by completely different catalytic mechanisms. Hierarchy of proteases Based on catalytic residue Proteases can be classified into seven broad groups: * Serine protease ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Zymogen
In biochemistry, a zymogen (), also called a proenzyme (), is an inactive precursor of an enzyme. A zymogen requires a biochemical change (such as a hydrolysis reaction revealing the active site, or changing the configuration to reveal the active site) for it to become an active enzyme. The biochemical change usually occurs in Golgi bodies, where a specific part of the precursor enzyme is cleaved in order to activate it. The inactivating piece which is cleaved off can be a peptide unit, or can be independently-folding domains comprising more than 100 residues. Although they limit the enzyme's ability, these N-terminal extensions of the enzyme or a “prosegment” often aid in the stabilization and folding of the enzyme they inhibit. The pancreas secretes zymogens partly to prevent the enzymes from digesting proteins in the cells in which they are synthesised. Enzymes like pepsin are created in the form of pepsinogen, an inactive zymogen. Pepsinogen is activated when chief ce ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Factor XII
Coagulation factor XII, also known as Hageman factor, is a plasma protein. It is the zymogen form of factor XIIa, an enzyme () of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by the ''F12'' gene. Structure Human Factor XII is 596 amino acids long and consists of two chains, the heavy chain (353 residues) and light chain (243 residues) held together by a disulfide bond. It is 80,000 daltons. Its heavy chain contains two fibronectin-type domains (type I and II), two epidermal growth factor-like domains, a kringle domain, and a proline-rich region, and its light chain contains the protease domain. The structure of the FnI-EGF-like tandem domain of coagulation factor XII has been solved by X-ray crystallography. Crystal structures of the FXII light chain has also been determined unbound (β-FXII) and bound (β-FXIIa) to inhibitors. Factor XII (FXII, Hageman factor) is a plasma glycoprotein of approximately 90 kDa molecular weight is part ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Contact Activation System
In the contact activation system or CAS, three proteins in the blood, factor XII (FXII), prekallikrein (PK) and high molecular weight kininogen (HK), bind to a surface and cause blood coagulation and inflammation. FXII and PK are proteases and HK is a non-enzymatic co-factor. The CAS can activate the kinin–kallikrein system and blood coagulation through its ability to activate multiple downstream proteins. The CAS is initiated when FXII binds to a surface and reciprocal activation of FXII and PK occurs, forming FXIIa and PKa. FXIIa can initiate the coagulation cascade by cleaving and activating factor XI (FXI), which leads to formation of a blood clot. Additionally, the CAS can activate the kinin–kallikrein system when PKa cleaves HK to form cHK, releasing a peptide known as bradykinin (BK). BK and its derivatives bind to bradykinin receptors B1 and B2 to mediate inflammation. Surfaces and activation Artificial negatively charged substances that activate FXII include L-homocy ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cystatin
The cystatins are a family of cysteine protease inhibitors which share a sequence homology and a common tertiary structure of an alpha helix lying on top of an anti-parallel beta sheet. The family is subdivided as described below. Cystatins show similarity to fetuins, kininogens, histidine-rich glycoproteins and cystatin-related proteins. Cystatins mainly inhibit peptidase enzymes (another term for ''proteases'') belonging to peptidase families C1 (papain family) and C13 ( legumain family). They are known to mis-fold to form amyloid deposits and are implicated in several diseases. Types The cystatin family includes: * The Type 1 cystatins, which are intracellular and are present in the cytosol of many cell types, but can also appear in body fluids at significant concentrations. They are single-chain polypeptides of about 100 residues, which have neither disulfide bonds nor carbohydrate side-chains. Type 1 cystatins are also known as Stefins (after the Stefan Institute where t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Prekallikrein
Prekallikrein (PK), also known as Fletcher factor, is an 85,000 Mr serine protease that complexes with high-molecular-weight kininogen. PK is the precursor of plasma kallikrein, which is a serine protease that activates kinins. PK is cleaved to produce kallikrein by activated Factor XII (Hageman factor). Structure Prekallikrein is homologous to factor XI, and similarly consists of four apple domains and a fifth, catalytic serine protease domain. The four apple domains create a disk-like platform around the base of the catalytic domain. However, unlike factor XI, prekallikrein does not form dimers. Prekallikrein is activated to form kallikrein by factor XII cleavage of a bond homologous to the corresponding bond cleaved during factor XI activation. Prekallikrein deficiency Hereditary deficiencies in PK are very rare. They can cause a prolonged APTT, which can be corrected by incubation of the patient’s plasma. Deficiencies in PK can also be acquired due to some disease st ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
