Defibrinogenating Agent
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Venombin A (, ''alpha-fibrinogenase'', ''habutobin'', ''zinc metalloproteinase Cbfib1.1'', ''zinc metalloproteinase Cbfib1.2'', ''zinc metalloproteinase Cbfib2'', ''
ancrod Ancrod (current brand name: Viprinex) is a defibrinogenating agent derived from the venom of the Malayan pit viper. Defibrinogenating blood produces an anticoagulant effect. Ancrod is not approved or marketed in any country. It is a thrombin-li ...
'') is an
enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
. This enzyme catalyses the following
chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
: Selective cleavage of Arg- bond in
fibrinogen Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood clo ...
, to form
fibrin Fibrin (also called Factor Ia) is a fibrous, non-globular protein involved in the clotting of blood. It is formed by the action of the protease thrombin on fibrinogen, which causes it to polymerize. The polymerized fibrin, together with platele ...
, and release
fibrinopeptide A The fibrinopeptides, fibrinopeptide A (FpA) and fibrinopeptide B (FpB), are peptides which are located in the central region of the fibrous glycoprotein fibrinogen (factor I) and are cleaved by the enzyme thrombin (factor IIa) to convert fibri ...
. The specificity of further degradation of fibrinogen varies with species origin of the enzyme This enzyme is a
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- ...
-like enzyme from
venom Venom or zootoxin is a type of toxin produced by an animal that is actively delivered through a wound by means of a bite, sting, or similar action. The toxin is delivered through a specially evolved ''venom apparatus'', such as fangs or a sti ...
s of
snake Snakes are elongated, Limbless vertebrate, limbless, carnivore, carnivorous reptiles of the suborder Serpentes . Like all other Squamata, squamates, snakes are ectothermic, amniote vertebrates covered in overlapping Scale (zoology), scales. Ma ...
s of the
viper The Viperidae (vipers) are a family of snakes found in most parts of the world, except for Antarctica, Australia, Hawaii, Madagascar, and various other isolated islands. They are venomous and have long (relative to non-vipers), hinged fangs tha ...
/
rattlesnake Rattlesnakes are venomous snakes that form the genera ''Crotalus'' and ''Sistrurus'' of the subfamily Crotalinae (the pit vipers). All rattlesnakes are vipers. Rattlesnakes are predators that live in a wide array of habitats, hunting small anim ...
group. Examples include
ancrod Ancrod (current brand name: Viprinex) is a defibrinogenating agent derived from the venom of the Malayan pit viper. Defibrinogenating blood produces an anticoagulant effect. Ancrod is not approved or marketed in any country. It is a thrombin-li ...
and
batroxobin Batroxobin, also known as reptilase, is a snake venom enzyme with Venombin A activity produced by '' Bothrops atrox'' and '' Bothrops moojeni'', venomous species of pit viper found east of the Andes in South America. It is a hemotoxin which acts ...
, two
serine protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. ...
s from snakes that have been used in medical preparations.


Applications

Venombin A enzymes are the sole representatives of the defibrinogenating agent class of drugs, which by its protease action removes
fibrinogen Fibrinogen (factor I) is a glycoprotein complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted enzymatically by thrombin to fibrin and then to a fibrin-based blood clo ...
from the circulation. They are thought to act as an
antithrombotic An antithrombotic agent is a drug that reduces the formation of blood clots (thrombi).http://cancerweb.ncl.ac.uk/cgi-bin/omd?antithrombotic Antithrombotics can be used therapeutically for prevention (primary prevention, secondary prevention) or tr ...
by depletion of fibrinogen. They are different from thrombin in that they only cleave
fibrinogen alpha chain Fibrinogen alpha chain is a protein that in humans is encoded by the ''FGA'' gene. Function The protein encoded by this gene is the alpha component of fibrinogen, a blood-borne glycoprotein composed of three pairs of nonidentical polypeptide c ...
(those do cleave both chains are called
venombin AB Venombin AB (, ''gabonase'', ''okinaxobin II'', ''Bitis gabonica venom serine proteinase'', ''afaâ'', ''cytin'') is an enzyme. This enzyme catalyses the following chemical reaction : Selective cleavage at Arg- bonds in fibrinogen to form fibrin ...
), which will end up only producing weak, urea-soluble microthrombi that is easily removed by
plasmin Plasmin is an important enzyme () present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein (in the zymogen form of plasminogen) is encode ...
. Their benefit in acute ischaemic stroke is not supported by available evidence. Alternatively, batroxobin is also used as a topical
hemostatic An antihemorrhagic (antihæmorrhagic) agent is a substance that promotes hemostasis (stops bleeding). It may also be known as a hemostatic (also spelled haemostatic) agent. Antihemorrhagic agents used in medicine have various mechanisms of action: ...
by its rapid local clot-expansion action.


References


External links

* {{Antithrombotics Antithrombotic enzymes EC 3.4.21 Antihemorrhagics