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Encyclopedia > Von Willebrand factor

Von Willebrand factor is a blood glycoprotein of the coagulation system. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome. Red blood cells (erythrocytes) are present in the blood and help carry oxygen to the rest of the cells in the body Blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). ... A glycoprotein is a macromolecule composed of a protein and a carbohydrate (a sugar). ... The coagulation of blood is a complex process during which blood forms solid clots. ... Von Willebrands disease (vWD) is the most common hereditary coagulation abnormality described in humans. ... Thrombotic thrombocytopenic purpura (TTP or Moschcowitz disease) is a rare disorder of the blood coagulation system that in most cases arises from the deficiency or inhibition of the enzyme responsible for cleaving von Willebrand factor. ... Heydes syndrome is a syndrome of aortic valve stenosis associated with gastrointestinal bleeding from colonic angiodysplasia. ... In medicine, Hemolytic-uremic syndrome (or haemolytic-uraemic syndrome, abbreviated HUS) is a disease characterised by microangiopathic hemolytic anemia, acute renal failure and a low platelet count (thrombocytopenia). ...

Contents


Biochemistry

Synthesis

vWF is a large multimeric glycoprotein present in blood plasma and produced constitutively in endothelium (in the Weibel-Palade bodies), megakaryocytes (α-granules of platelets), and subendothelial connective tissue. A glycoprotein is a macromolecule composed of a protein and a carbohydrate (a sugar). ... Blood plasma is the liquid component of blood, in which the blood cells are suspended. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... In physiology, Weibel-Palade bodies are organelles in the endothelium, the cells lining all blood vessels. ... The megakaryocyte is a bone marrow cell responsible for the production of blood platelets when cytoplasm processes become fragmented. ... A 250 ml bag of newly collected platelets. ... Connective tissue is any type of biological tissue with an extensive extracellular matrix and often serves to support, bind together, and protect organs. ...


Structure

The basic vWF monomer is a 2050 amino acid protein. Every monomer contains a number of specific domains with a specific function; elements of note are: Image File history File links VWF.png Von Willebrand factor mono- and multimer structure Permission is granted to copy, distribute and/or modify this document under the terms of the GNU Free Documentation License, Version 1. ... In chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. ...

Monomers are subsequently N-glycosylated, arranged into dimers in the endoplasmic reticulum and into multimers in the Golgi apparatus by crosslinking of cysteine residues via disulfide bonds. With respect to the glycosylation, vWF is one of the few proteins that carry blood group antigens (ABO system). A 250 ml bag of newly collected platelets. ... Heparin - Wikipedia, the free encyclopedia /**/ @import /skins-1. ... Tropocollagen triple helix. ... Arginine (Arg) is an α-amino acid. ... Glycine (Gly, G) is a nonpolar amino acid. ... Asparagine is one of the 20 most common natural amino acids on Earth. ... An integrin, or integrin receptor, is an integral membrane protein in the plasma membrane of cells. ... Platelet-derived growth factor (PDGF) is one of the numerous proteins that regulate cell growth and division. ... Transforming growth factor (TGF) is one of many characterized growth factors that exist in nature. ... Human chorionic gonadotropin (hCG) is a peptide hormone produced in pregnancy, that is made by the embryo soon after conception and later by the trophoblast (part of the placenta). ... A pregnancy test is a test to determine whether or not a woman is pregnant. ... Glycosylation is the process or result of addition of saccharides to proteins and lipids. ... The endoplasmic reticulum or ER (endoplasmic means within the cytoplasm, reticulum means little net) is an organelle found in all eukaryotic cells. ... In cell biology, the Golgi apparatus (also called a Golgi body, Golgi complex, or dictyosome) is an organelle found in most eukaryotic cells, including those of plants, animals, and fungi. ... Cysteine is a naturally occurring hydrophobic amino acid which has a thiol group and is found in most proteins, though only in small quantities. ... A disulfide bond (SS-bond), also called a disulfide bridge, is a strong covalent bond between two sulfhydryl groups. ... A blood type is a description an individuals characteristics of red blood cells due to substances (carbohydrates and proteins) on the cell membrane. ...


Multimers of vWF can be extremely large, >20,000 kDa, and consist of over 80 subunits of 250 kDa each. Only the large multimers are functional. Some cleavage products that result from vWF production are also secreted but probably serve no function. The Kampfgruppen der Arbeiterklasse (German: Combat Groups of the Working Class) was a paramilitary organisation in East Germany, founded in 1953 and abolished in 1990. ...


Function

Von Willebrand factor is not an enzyme and therefore has no catalytic activity. Its primary functions is binding to other proteins, particularly Factor VIII and it is important in platelet adhesion to wound sites. Ribbon diagram of the catalytically perfect enzyme TIM. An enzyme is a protein that catalyzes, or speeds up, a chemical reaction. ...


vWF binds to a number of cells and molecules. The most important ones are:

  • Factor VIII is bound to vWF whilst inactive in circulation; Factor VIII degrades rapidly when not bound to vWF. Factor VIII is released form vWF by the action of thrombin.
  • vWF binds to collagen, e.g., when it is exposed in endothelial cells due to damage occurring to the blood vessel.
  • vWF binds to platelet gpIb when it forms a complex with gpIX and gpV; this binding occurs under all circumstances, but is most efficient under high shear stress (i.e., rapid blood flow in narrow blood vessels, see below).
  • vWF binds to other platelet receptors when they are activated, e.g., by thrombin (i.e., when coagulation has been stimulated).

vWF appears to play a major role blood coagulation, and vWF deficiency or dysfunction (von Willebrand disease) therefore leads to a bleeding tendency, which is most apparent in tissues having high blood flow shear in narrow vessels. From studies it appears that vWF uncoils under these circumstances, decelerating passing platelets. Thrombin (activated Factor II) is a coagulation protein that has many effects in the coagulation cascade. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... A glycoprotein is a macromolecule composed of a protein and a carbohydrate (a sugar). ... Shear stress is a stress state where the shape of a material tends to change (usually by sliding forces -- torque by transversely-acting forces) without particular volume change. ... Thrombin (activated Factor II) is a coagulation protein that has many effects in the coagulation cascade. ... In physics and mechanics, shear refers to a deformation that causes parallel surfaces to slide past one another (as opposed to compression and tension, which cause parallel surfaces to move towards or away from one another). ...


Catabolism

The biological breakdown (catabolism) of vWF is largely mediated by a protein cryptically termed ADAMTS13 (acronym of "a disintegrin-like and metalloprotease with thrombospondin type 1 motif no. 13"). It is a metalloproteinase which cleaves vWF between tyrosine at position 842 and methionine at position 843 (or 1605-1606 of the gene). This breaks down the multimers into smaller units, which are degraded by other peptidases. Anabolism is the aspect of metabolism that contributes to growth. ... ADAMTS13 (A Disintegrin And Metalloproteinase with a ThromboSpondin type 1 motif, member 13) is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting. ... The metalloendopeptidases (also called metalloproteinases or metalloproteases) are a class of enzymes from the group of endopeptidases. ... Proteolysis is the directed degradation (digestion) of proteins by cellular enzymes called proteases or by intramolecular digestion. ... Tyrosine (from the Greek tyros, meaning cheese, as it was first discovered in cheese), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid, is one of the 20 amino acids that are used by cells to synthesize proteins. ... Methionine (Met, M. C5H11NO2S) is an essential nonpolar amino acid, and a lipotropic. ... Peptidases (proteases [pronounced pro-tea-aces] and proteolytic enzymes are also commonly used) are enzymes which break peptide bonds of proteins. ...


Role in disease

A genetic disorder, or genetic disease is a disease caused by abnormal expression of one or more genes in a person causing a clinical phenotype. ... In medicine (hematology), a bleeding diathesis is a propensity to bleeding (hemorrhage) due to a defect in the system of coagulation. ... Nosebleed as a result of fracture through a rugby impact. ... Menorrhagia is an abnormally heavy and prolonged menstrual periods. ... Gastrointestinal bleeding describes every form of hemorrhage (blood loss) in the gastrointestinal tract, from the pharynx to the rectum. ... In biology, mutations are changes to the genetic material (usually DNA or RNA). ... Heydes syndrome is a syndrome of aortic valve stenosis associated with gastrointestinal bleeding from colonic angiodysplasia. ... In medicine (gastroenterology), angiodysplasia is a small vascular malformation of the gut. ... Grays Fig. ... Aortic valve stenosis (AS) is a heart condition caused by the incomplete opening of the aortic valve. ... Thrombotic thrombocytopenic purpura (TTP or Moschcowitz disease) is a rare disorder of the blood coagulation system that in most cases arises from the deficiency or inhibition of the enzyme responsible for cleaving von Willebrand factor. ... Schematic of antibody binding to an antigen An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... In medicine (hematology) microangiopathic hemolytic anemia (MAHA) is a subgroup of hemolytic anemia (anemia, loss of red blood cells through destruction) caused by factors in the small blood vessels. ...

History

vWF is named after Dr. Erik von Willebrand, a Finnish doctor who in 1924 first described a hereditary bleeding disorder in families from the Åland islands who had a tendency for cutaneous and mucosal bleeding, including menorrhagia. Although von Willebrand could not identify the definite cause, he distinguished von Willebrand disease (vWD) from haemophilia and other forms of bleeding diathesis. 1924 (MCMXXIV) was a leap year starting on Tuesday (link will take you to calendar). ... Motto: None Anthem: Ã…länningens sÃ¥ng Capital Mariehamn Largest city Mariehamn Official language(s) Swedish Government Governor Premier Autonomous Province Peter Lindbäck Roger Nordlund Autonomy 1920 Area  â€¢ Total  â€¢ Water (%)   6,784 km² (n/a) 77. ... Menorrhagia is an abnormally heavy and prolonged menstrual periods. ... Haemophilia or hemophilia is the name of any of several hereditary genetic illnesses that impair the bodys ability to control bleeding. ... In medicine (hematology), a bleeding diathesis is a propensity to bleeding (hemorrhage) due to a defect in the system of coagulation. ...


In the 1950s, vWD was shown to be caused by a plasma factor deficiency (instead of being caused by platelet disorders), and, in the 1970s, the vWF protein was purified. // Events and trends This map shows two essential global spheres during the Cold War in 1959. ... The 1970s decade refers to the years from 1970 to 1979, inclusive. ...


Sources

  • Sadler, J. E. Biochemistry and Genetics of von Willebrand factor. Annu Rev Biochem 1998; 67: 395-424. PMID 9759493.

See also


Von Willebrands disease (vWD) is the most common hereditary coagulation abnormality described in humans. ...

Coagulation
Coagulation factors: - Fibrin (I) - (Pro)thrombin (II) - FV - FVII - FVIII - FIX - FX - FXI - FXII - FXIII - HMWK - vWF - Thromboplastin
Inhibitors: Antithrombin - Protein C - Protein S - Protein Z - ZPI - TFPI
Fibrinolysis: Plasmin - tPA/urokinase - PAI-1/2 - α2-AP - TAFI

  Results from FactBites:
 
eMedicine - Von Willebrand Disease : Article by John D Geil, MD (3590 words)
VWF activity (ristocetin cofactor): Ristocetin is an antibiotic that causes VWF to bind to and, subsequently, to activate platelets.
The degree of platelet agglutination is proportional to the concentration of VWF in the plasma.
Sadler JE: A revised classification of von Willebrand disease.
Von Willebrand's Disease (1066 words)
Von Willebrand's factor is a glycoprotein produced both by platelets (the blood cells involved in clotting) and by the cells lining blood vessels.
Von Willebrand's disease is not limited to the breeds listed here; forms of von Willebrand's disease have been found in over 50 breeds and in cats and humans as well.
Von Willebrand's disease is usually detected when there is unexpected hemorrhage during a spay or neuter or when screening tests are done in anticipation of surgery on a member of a von Willebrand's breed.
  More results at FactBites »

 
 

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