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The composition of snake venom differs from species to species. There is also variation within a single species depending on age, season and temperature. It is a complex mixture of enzymes, toxins and all sorts of smaller molecules. The most important components are the substances with a cytotoxic effect, the neurotoxins and the coagulants. Some toxins have multiple effects. The function of some components is still a mystery. For example, "nerve growth factor" was isolated from cobra venom. This protein, discovered by Rita Levi-Montalcini and Stanley Cohen (Nobel Prize 1986), plays a major role in the growth of nerve tissue, yet why this molecule is present at high concentration in venom in the first place remains an open question. Possibly it promotes the absorption of venom by releasing various mediators from mastocytes.
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Note: Nerve growth factor
Nerve growth factor (NGF) is the prototype for the neurotrophin family of polypeptides which are essential in the developments and survival of certain sympathetic and sensory neurons in both the central and peripheral nervous systems. NGF was discovered when mouse sarcoma tissue transplants in chicken embryos caused an increase in the size of spinal ganglia. In the course of attempting to characterise the agent responsible for this action, cobra venom, employed as a phosphodiesterase, was found to found to give unexpected similar results. It was proven to be a rich source of NGF. A homologous tissue, the submaxillary gland of adult male mice, has become the preferred source of NGF. Other unusually large concentrations are found in the guinea pig prostate gland and in bovine seminal plasma. The physiological relevance of these sources is not fully understood.
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Enzymes, which help the snake to digest its prey, are often cytotoxic for man. Proteolytic enzymes have a trypsin-like activity. Hyaluronidase splits acidic mucopolysaccharides and promotes the distribution of venom in the extracellular matrix of connective tissue. Snake venom often contains various phospholipases A2. These are esterolytic enzymes which break down membrane phospholipids such as lecithin (= phosphatidylcholine) into fatty acids and lysolecithin. This causes cellular membrane damage ("lyso" ® lysis: destroy). In human beings, all these enzymes cause oedema, blister formation and local tissue necrosis.
With regard to function, the neurotoxins of some elapids can be compared with curare or with the autoantibodies in myasthenia gravis. The neurotoxins block the stimulus transmission from nerve cell to muscle and cause paralysis. The venom does not penetrate the blood-brain barrier. Some venom (cobra, mamba, death adder, Laticauda, krait alpha-bungarotoxin) works on the nicotinic acetylcholine receptor present on muscle (neuromuscular junction). The postsynaptic effects are reversible with antivenom and neostigmin. Other types of venom work on the presynaptic nerve terminal, e.g. beta-bungarotoxin) and here neostigmin will not be effective. Presynaptic neurotoxins inhibit the fusion of the vesicles containing acetylcholine, with the nerves membrane of the neuromuscular junction.
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Note:Curare
Curare is a complex alkaloid which is derived from South American plants such as Chondodendron tomentosum (tubocurarine) and Strychnos toxifera. It acts on the postsynaptic acetylcholine-receptor of the neuromuscular junction and causes paralysis. The mechanism is comparable to elapid venom.
Snake venom can interfere with blood coagulation. Several of the enzymes contained in such venoms can be used in the laboratory in coagulation studies. Venom can either activate prothrombin (e.g. ecarin from Echis carinatus) or have a direct effect on fibrinogen and convert it into fibrin and thus itself have a thrombin-like activity, such as crotalase (rattlesnake venom), ancrod from Calloselamsa rhodostoma and batroxobin (reptilase) from Bothrops atrox moojeni. Such enzymes with a thrombin-activity are insensitive to heparin and can be used for defibrination of heparinized blood samples. In the laboratory, the reptilase time is an alternative to the thrombin time in such samples. Certain enzymes in venom activate factor V (e.g. Russellīs viper and Vipera lebetina), activate factor X (e.g. Russellīs viper; used in Stypven time) or promote fibrinolysis (e.g. the enzyme lebetase from V. lebetina). Diluted venom of Russellīs viper contains a specific activator of factor X which is used in some laboratory tests for lupus anticoagulant ("dRVVT or dilute Russellīs Viper Venom Time"). Fibrin will normally be dissolved rather quickly by plasmin via the fibrinolytic system. Some components of snake venom interfere with fibrinolysis. Sometimes venom causes direct aggregation of blood platelets (rattlesnakes) or, on the contrary, an inhibition of such aggregation (Levantine viper). Convulxin is a component of Crotalus durissus terrificus venom. This substance binds selectively and with high affinity to blood platelets through a mechanism that resembles exposure to collagen (convulxin attaches itself to the collagen receptor glycoprotein VI). Endothelial damage can be caused by venom containing so-called "haemorrhagins". This produces a propensity to haemorrhage. Several snakes can activate protein C. Protac is the responsible enzyme in Agkistrodon contortrix. It can be used in certain coagulation tests in the laboratory, such as analysis of the protein C/S system. Botrocetin coming from the venom of Bothrops jararaca is sometimes used for studying blood platelets and von Willebrand factor. It is in this respect somewhat comparable to ristocetin (antibiotic from Nocardia lurida).
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Note: Proposed nomenclature
Proposed nomenclature of the suffixes which indicate a haemostatic effect for exogenous factors (is not always followed, however):
