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A protease is an enzyme that catalyzes 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, and cell signaling.
Von Willebrand disease (VWD) is the most common hereditary blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of von Willebrand factor (VWF), a multimeric protein that is required for platelet adhesion. It is known to affect several breeds of dogs as well as humans. The three forms of VWD are hereditary, acquired, and pseudo or platelet type. The three types of hereditary VWD are VWD type 1, VWD type 2, and VWD type 3. Type 2 contains various subtypes. Platelet type VWD is also an inherited condition.
Thrombotic thrombocytopenic purpura (TTP) is a blood disorder that results in blood clots forming in small blood vessels throughout the body. This results in a low platelet count, low red blood cells due to their breakdown, and often kidney, heart, and brain dysfunction. Symptoms may include large bruises, fever, weakness, shortness of breath, confusion, and headache. Repeated episodes may occur.
Heyde's syndrome is a syndrome of gastrointestinal bleeding from angiodysplasia in the presence of aortic stenosis.
Von Willebrand factor (VWF) is a blood glycoprotein involved in hemostasis, specifically, platelet adhesion. It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic–uremic syndrome. Increased plasma levels in many cardiovascular, neoplastic, metabolic, and connective tissue diseases are presumed to arise from adverse changes to the endothelium, and may predict an increased risk of thrombosis.
Weibel–Palade bodies (WPBs) are the storage granules of endothelial cells, the cells that form the inner lining of the blood vessels and heart. They manufacture, store and release two principal molecules, von Willebrand factor and P-selectin, and thus play a dual role in hemostasis and inflammation.
Factor X, also known by the eponym Stuart–Prower factor, is an enzyme of the coagulation cascade. It is a serine endopeptidase. Factor X is synthesized in the liver and requires vitamin K for its synthesis.
The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. For human blood transfusions, it is the most important of the 44 different blood type classification systems currently recognized by the International Society of Blood Transfusions (ISBT) as of December 2022. A mismatch in this, or any other serotype, can cause a potentially fatal adverse reaction after a transfusion, or an unwanted immune response to an organ transplant. The associated anti-A and anti-B antibodies are usually IgM antibodies, produced in the first years of life by sensitization to environmental substances such as food, bacteria, and viruses.
ADAMTS13 —also known as von Willebrand factor-cleaving protease (VWFCP)—is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor (vWf), a large protein involved in blood clotting. It is secreted into the blood and degrades large vWf multimers, decreasing their activity.
A disintegrin and metalloproteinase with thrombospondin motifs 2 (ADAM-TS2) also known as procollagen I N-proteinase is an enzyme that in humans is encoded by the ADAMTS2 gene.
Furin is a protease, a proteolytic enzyme that in humans and other animals is encoded by the FURIN gene. Some proteins are inactive when they are first synthesized, and must have sections removed in order to become active. Furin cleaves these sections and activates the proteins. It was named furin because it was in the upstream region of an oncogene known as FES. The gene was known as FUR and therefore the protein was named furin. Furin is also known as PACE. A member of family S8, furin is a subtilisin-like peptidase.
ADAMs are a family of single-pass transmembrane and secreted metalloendopeptidases. All ADAMs are characterized by a particular domain organization featuring a pro-domain, a metalloprotease, a disintegrin, a cysteine-rich, an epidermal-growth factor like and a transmembrane domain, as well as a C-terminal cytoplasmic tail. Nonetheless, not all human ADAMs have a functional protease domain, which indicates that their biological function mainly depends on protein–protein interactions. Those ADAMs which are active proteases are classified as sheddases because they cut off or shed extracellular portions of transmembrane proteins. For example, ADAM10 can cut off part of the HER2 receptor, thereby activating it. ADAM genes are found in animals, choanoflagellates, fungi and some groups of green algae. Most green algae and all land plants likely lost ADAM proteins.
Aspartic proteases are a catalytic type of protease enzymes that use an activated water molecule bound to one or more aspartate residues for catalysis of their peptide substrates. In general, they have two highly conserved aspartates in the active site and are optimally active at acidic pH. Nearly all known aspartyl proteases are inhibited by pepstatin.
Platelet glycoprotein Ib alpha chain also known as glycoprotein Ib (platelet), alpha polypeptide or CD42b, is a protein that in humans is encoded by the GP1BA gene.
Kexin is a prohormone-processing protease, specifically a yeast serine peptidase, found in the budding yeast. It catalyzes the cleavage of -Lys-Arg- and -Arg-Arg- bonds to process yeast alpha-factor pheromone and killer toxin precursors. The human homolog is PCSK4. It is a family of subtilisin-like peptidases. Even though there are a few prokaryote kexin-like peptidases, all kexins are eukaryotes. The enzyme is encoded by the yeast gene KEX2, and usually referred to in the scientific community as Kex2p. It shares structural similarities with the bacterial protease subtilisin. The first mammalian homologue of this protein to be identified was furin. In the mammal, kexin-like peptidases function in creating and regulating many differing proproteins.
ADAMTS is a family of multidomain extracellular protease enzymes. 19 members of this family have been identified in humans, the first of which, ADAMTS1, was described in 1997. Known functions of the ADAMTS proteases include processing of procollagens and von Willebrand factor as well as cleavage of aggrecan, versican, brevican and neurocan, making them key remodeling enzymes of the extracellular matrix. They have been demonstrated to have important roles in connective tissue organization, coagulation, inflammation, arthritis, angiogenesis and cell migration. Homologous subfamily of ADAMTSL (ADAMTS-like) proteins, which lack enzymatic activity, has also been described. Most cases of thrombotic thrombocytopenic purpura arise from autoantibody-mediated inhibition of ADAMTS13.
A disintegrin and metalloproteinase with thrombospondin motifs 3 is an enzyme that in humans is encoded by the ADAMTS3 gene. The protein encoded by this gene is the major procollagen II N-propeptidase.
Angiogenesis is the process of forming new blood vessels from existing blood vessels, formed in vasculogenesis. It is a highly complex process involving extensive interplay between cells, soluble factors, and the extracellular matrix (ECM). Angiogenesis is critical during normal physiological development, but it also occurs in adults during inflammation, wound healing, ischemia, and in pathological conditions such as rheumatoid arthritis, hemangioma, and tumor growth. Proteolysis has been indicated as one of the first and most sustained activities involved in the formation of new blood vessels. Numerous proteases including matrix metalloproteinases (MMPs), a disintegrin and metalloproteinase domain (ADAM), a disintegrin and metalloproteinase domain with throbospondin motifs (ADAMTS), and cysteine and serine proteases are involved in angiogenesis. This article focuses on the important and diverse roles that these proteases play in the regulation of angiogenesis.
ADAMTS-4 endopeptidase is an enzyme. This enzyme catalyses the following chemical reaction
Upshaw–Schulman syndrome (USS) is the recessively inherited form of thrombotic thrombocytopenic purpura (TTP), a rare and complex blood coagulation disease. USS is caused by the absence of the ADAMTS13 protease resulting in the persistence of ultra large von Willebrand factor multimers (ULVWF), causing episodes of acute thrombotic microangiopathy with disseminated multiple small vessel obstructions. These obstructions deprive downstream tissues from blood and oxygen, which can result in tissue damage and death. The presentation of an acute USS episode is variable but usually associated with thrombocytopenia, microangiopathic hemolytic anemia (MAHA) with schistocytes on the peripheral blood smear, fever and signs of ischemic organ damage in the brain, kidney and heart.
References
- ↑ Fujikawa K, Suzuki H, McMullen B, Chung D (September 2001). "Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family". Blood. 98 (6): 1662–6. doi: 10.1182/blood.v98.6.1662 . PMID 11535495.
- ↑ Dong JF, Moake JL, Nolasco L, Bernardo A, Arceneaux W, Shrimpton CN, Schade AJ, McIntire LV, Fujikawa K, López JA (December 2002). "ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions". Blood. 100 (12): 4033–9. doi: 10.1182/blood-2002-05-1401 . PMID 12393397.
