| Snake toxin | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| Symbol | Toxin_1 | ||||||||
| Pfam | PF00087 | ||||||||
| InterPro | IPR003571 | ||||||||
| PROSITE | PDOC00245 | ||||||||
| SCOP | 2ctx | ||||||||
| OPM family | 55 | ||||||||
| OPM protein | 1txa | ||||||||
|
|||||||||
Snake venom is highly modified saliva.[1] The venom is part of a whole - the apparatus: which is made up of venom glands that synthesize venom and an injection system: modified fangs with which to make the venom penetrate into a prey item or a possible threat or predator.[2] The glands which secrete the zootoxins are a modification of the parotid salivary gland of other vertebrates, and are usually situated on each side of the head below and behind the eye, encapsulated in a muscular sheath. The glands have large alveoli in which the synthesized venom is stored before being conveyed by a duct to the base of channeled or tubular fangs, through which it is ejected. Venoms contain more than 20 different compounds, mostly proteins and polypeptides.[3][4] Snake venom has two main functions: first, the immobilization of prey and second, the digestion of prey. It is a complex mixture of proteins, enzymes, and various other substances. The proteins are responsible for the toxic and lethal effect of the venom[2] and its function is to immobilize prey,[5] enzymes play an important role in the digestion of prey,[4] and various other substances are responsible for important but non-lethal biological effects.[2] Some of the proteins in snake venom are very particular in their effects on various biological functions including blood coagulation, blood pressure regulation, transmission of the nervous or muscular impulse and have turned out to be pharmacological or diagnostic tools or even useful drugs.[2]
Contents |
Lucien Bonaparte, the younger brother of Napoleon Bonaparte was the first to establish the proteinaceous nature of snake venom in 1843. Proteins constitute 90-95% of venom's dry weight and they are responsible for almost all of its biological effects. Among hundreds, even thousands of proteins found in venom, there are toxins, neurotoxins in particular, as well as nontoxic proteins (which also have pharmacological properties), and many enzymes, especially hydrolithic ones.[2] Enzymes (molecular weight 13-150 KDa) make-up 80-90% of viperid and 25-70% of elapid venoms: digestive hydrolases, L-amino acid oxidase, phospholipases, thrombin-like pro-coagulant, and kallikrein-like serine proteases and metalloproteinases (hemorrhagins), which damage vascular endothelium. Polypeptide toxins (molecular weight 5-10 KDa) include cytotoxins, cardiotoxins, and postsynaptic neurotoxins (such as α-bungarotoxin and α-Cobratoxin), which bind to acetylcholine receptors at neuromuscular junctions. Compounds with low molecular weight (up to 1.5 KDa) include metals, peptides, lipids, nucleosides, carbohydrates, amines, and oligopeptides, which inhibit angiotensin converting enzyme (ACE) and potentiate bradykinin (BPP). Inter- and intra-species variation in venom chemical composition is geographical and ontogenic.[3] Phosphodiesterases interfere with the prey's cardiac system, mainly to lower the blood pressure. Phospholipase A2 causes hemolysis by lysing the phospholipid cell membranes of red blood cells.[6] Amino acid oxidases and proteases are used for digestion. Amino acid oxidase also triggers some other enzymes and is responsible for the yellow colour of the venom of some species. Hyaluronidase increases tissue permeability to accelerate absorption of other enzymes into tissues. Some snake venoms carry fasciculins, like the mambas (Dendroaspis), which inhibit cholinesterase to make the prey lose muscle control.[7]
| Type | Name | Origin |
| Oxydoreductases | dehydrogenase lactate | Elapidae |
| L-amino-acid oxidase | All species | |
| Catalase | All species | |
| Transferases | Alanine amino transferase | |
| Hydrolases | Phospholipase A2 | All species |
| Lysophospholipase | Elapidae, Viperidae | |
| Acetylcholinesterase | Elapidae | |
| Alkaline phosphatase | Bothrops atrox | |
| Acid phosphatase | Deinagkistrodon acutus | |
| 5'-Nucleotidase | All species | |
| Phosphodiesterase | All species | |
| Deoxyribonuclease | All species | |
| Ribonuclease 1 | All species | |
| Adenosine triphosphatase | All species | |
| Amylase | All species | |
| Hyaluronidase | All species | |
| NAD-Nucleotidase | All species | |
| Kininogenase | Viperidae | |
| Factor-X activator | Viperidae, Crotalinae | |
| Heparinase | Crotalinae | |
| α-Fibrinogenase | Viperidae, Crotalinae | |
| β-Fibrinogenase | Viperidae, Crotalinae | |
| α-β-Fibrinogenase | Bitis gabonica | |
| Fibrinolytic enzyme | Crotalinae | |
| Prothrombin activator | Crotalinae | |
| Collagenase | Viperidae | |
| Elastase | Viperidae | |
| Lyases | Glucosamine ammonium lyase |
Snake toxins vary greatly in their functions. Two major classifications of toxins found in snake venoms include neurotoxins (mostly found in elapids) and hemotoxins (mostly found in viperids). However, there are exceptions - an African spitting cobra Naja nigricollis's venom consists mainly of hemotoxins, while the Mojave rattlesnake's venom is primarily neurotoxic. However, there are numerous other different types of toxins which both elapids or viperids may carry.
| α-neurotoxins | α-Bungarotoxin, α-toxin, erabutoxin, cobratoxin |
|---|---|
| β-neurotoxins | Notexin, ammodytoxin, β-Bungarotoxin, crotoxin, taipoxin |
| κ-Toxins | κ-Toxin |
| Dendrotoxins | Dendrotoxin, toxins I and K |
| Cardiotoxins | y-Toxin, cardiotoxin, cytotoxin |
| Myotoxins | Myotoxin-a, crotamine |
| Sarafotoxins | Sarafotoxins a, b, and c |
| Hemorrhagins | Phospholipase A2, mucrotoxin A, hemorrhagic toxins a, b, c..., HT1, HT2 |
| Structure of a typical chemical synapse |
|---|
The beginning of a new impulse:
A) An exchange of ions (charged atoms) across the nerve cell membrane sends a depolarising current towards the end of the nerve cell (cell terminus).
B) When the depolarising current arrives at the nerve cell terminus, the neurotransmitter acetylcholine (ACh), which is held in vesicles, is released into the space between the two nerves (synapse). It moves across the synapse to the postsynaptic receptors.
C) If ACh remains at the receptor, the nerve stays stimulated, causing incontrollable muscle contractions. This condition is called tetany. An enzyme called acetylcholinesterase destroys the ACh so tetany does not occur.
Fasciculins:
These toxins attack cholinergic neurons (those that use ACh as a transmitter) by destroying acetylcholinesterase (AChE). ACh therefore cannot be broken down and stays in the receptor. This causes tetany, which can lead to death. The toxins have been called fasciculins since after injection into mice, they cause severe, generalized and long-lasting (5-7 h) fasciculations.
Snake example: found mostly in venom of Mambas and some rattlesnakes
Dendrotoxins inhibit neurotransmissions by blocking the exchange of + and – ions across the neuronal membrane lead to no nerve impulse. So they paralyse the nerves.
Snake example: Mambas
α-neurotoxins:
This is a large group of toxins, with over 100 postsynaptic neurotoxins having been identified and sequenced.[8] α-neurotoxins also attack cholinergic neurons. They mimic the shape of the acetylcholine molecule and therefore fit into the receptors → they block the ACh flow → feeling of numbness and paralysis.
Snake examples:
- King Cobra (known as hannahtoxin containing α-neurotoxins)[9]
- Sea snake (known as erabutoxin)
- Many-banded krait (known as α-Bungarotoxin)
- Cobras (known as cobratoxin),
Phospholipase is an enzyme that transforms the phospholipid molecule into a lysophospholipid (soap) ==> the new molecule attracts and binds fat and ruptures cell membranes.
Snake example: Japanese Habu
Cardiotoxins are components that are specifically toxic to the heart. They bind to particular sites on the surface of muscle cells and cause depolarisation ==> the toxin prevents muscle contraction. These toxins may cause the heart to beat irregularly or stop beating, causing death.
Snake example: King Cobra, Mambas, and some members of Naja genus
The toxin causes haemolysis, or destruction of red blood cells (erythrocytes).
Snake example: most Vipers and the many members of Naja genus
Snake cytotoxin IPR003572
The presence of enzymes in snake venom was once believed to be an adaptation to assist digestion. However, studies of the western diamondback rattlesnake, a snake with highly proteolytic venom, show that venom has no impact on the time required for food to pass through the gut. More research is needed to determine the selective pressures resulting in evolution of venom and venom delivery mechanisms.[10]
In the vipers, which have the most highly developed venom delivery apparatus, the venom gland is very large and is surrounded by the masseter or temporal muscle, which consists of two bands, the superior arising from behind the eye, the inferior extending from the gland to the mandible. A duct carries venom from the gland to the fang. In vipers and elapids, this groove is completely closed, forming a hypodermic needle-like tube. In other species, the grooves are not covered, or only partially covered. From the anterior extremity of the gland, the duct passes below the eye and above the maxillary bone, to the basal orifice of the venom fang, which is ensheathed in a thick fold of mucous membrane. By means of the movable maxillary bone hinged to the prefrontal bone and connected with the tranverse bone which is pushed forward by muscles set in action by the opening of the mouth, the fang is erected and the venom discharged through the distal orifice. When the snake bites, the jaws close and the muscles surrounding the gland contract, causing venom to be ejected via the fangs.
In the proteroglyphous elapids, the fangs are tubular, but are short and do not possess the mobility seen in vipers.
opisthoglyphous colubrids have enlarged, grooved teeth situated at the posterior extremity of the maxilla, where a small posterior portion of the upper labial or salivary gland produces venom.
Several genera, including Calliophis, Atractaspis and Causus, are remarkable for having exceptionally long venom glands, extending along each side of the body, in some cases extending posterially as far as the heart. Instead of the muscles of the temporal region serving to press out the venom into the duct, this action is performed by those of the side of the body.
There is considerable variability in biting behavior among snakes. When biting, viperid snakes often strike quickly, discharging venom as the fangs penetrate the skin, and then immediately release. Alternatively, as in the case of a feeding response, some viperids (e.g. Lachesis) will bite and hold. A proteroglyph or opisthoglyph, may close its jaws and bite or chew firmly for a considerable time.
Spitting cobras of the genera Naja and Hemachatus, when irritated or threatened, may eject streams or a spray of venom a distance of 4 to 8 feet. These snakes' fangs have been modified for the purposes of spitting: inside the fangs, the channel makes a ninety degree bend to the lower front of the fang. Spitters may spit repeatedly and still be able to deliver a fatal bite.
Spitting is a defensive reaction only. The snakes tend to aim for the eyes of a perceived threat. A direct hit can cause temporary shock and blindness through severe inflammation of the cornea and conjunctiva. Usually there are no serious results if the venom is washed away immediately with plenty of water, blindness can become permanent if left untreated. Brief contact with the skin is not immediately dangerous, but open wounds may be vectors for envenomation.
There are four distinct types of venom that act on the body differently.
It is noteworthy that the size of the venom fangs is in no relation to the virulence of the venom. The comparatively innocent Indo-Malay Lachesis alluded to above have enormous fangs, whilst the smallest fangs are found in the Hydrophids which possess very potent venom.
The effect of the venom of proteroglyphous snakes(Hydrophids, Bungarus, Dendroaspis, Elaps, Pseudechis, Notechis, Acanthophis) is mainly on the nervous system, respiratory paralysis being quickly produced by bringing the venom into contact with the central nervous mechanism which controls respiration; the pain and local swelling which follow a bite are not usually severe.
The bite of all the proteroglyphous elapids, even of the smallest and gentlest, such as the Elaps or coral snakes, is, so far as known, deadly to humans.
Viper venom (Daboia, Echis, Lachesis, Crotalus) acts more on the vascular system, bringing about coagulation of the blood and clotting of the pulmonary arteries; its action on the nervous system is not great, no individual group of nerve-cells appears to be picked out, and the effect upon respiration is not so direct; the influence upon the circulation explains the great depression which is a symptom of viperine envenomation. The pain of the wound is severe, and is speedily followed by swelling and discoloration. The symptoms produced by the bite of the European vipers are thus described by the best authorities on snake venom (Martin and Lamb):
The bite is immediately followed by local pain of a burning character; the limb soon swells and becomes discoloured, and within one to three hours great prostration, accompanied by vomiting, and often diarrhoea, sets in. Cold, clammy perspiration is usual. The pulse becomes extremely feeble, and slight dyspnoea and restlessness may be seen. In severe cases, which occur mostly in children, the pulse may become imperceptible and the extremities cold; the patient may pass into coma. In from twelve to twenty-four hours these severe constitutional symptoms usually pass off; but in the meantime the swelling and discoloration have spread enormously. The limb becomes phlegmonous, and occasionally suppurates. Within a few days recovery usually occurs somewhat suddenly, but death may result from the severe depression or from the secondary effects of suppuration. That cases of death, in adults as well as in children, are not infrequent in some parts of the Continent is mentioned in the last chapter of this Introduction.
The Viperidae differ much among themselves in the toxicity of their venom. Some, such as the Indian Daboia russelli and Echis carinatus; the American vipers Crotalus, Lachesis muta and Bothrops lanceolatus; and the African Causus, Bitis, and Cerastes, cause fatal results unless a remedy is speedily applied. On the other hand, the Indian and Malay Lachesis seldom cause the death of humans, their bite in some instances being no worse than the sting of a hornet. The bite of the larger European vipers may be very dangerous, and followed by fatal results, especially in children, at least in the hotter parts of the Continent; whilst the small Vipera ursinii, which hardly ever bites unless roughly handled, does not seem to be possessed of a very virulent venom, and, although very common in some parts of Austria-Hungary, is not known to have ever caused a serious accident.
Biologists had long known that some snakes had rear fangs, 'inferior' venom injection mechanisms that might immobilize prey; although a few fatalities were on record, until 1957 the possibility that such snakes were deadly to humans seemed at most remote. The deaths of two prominent herpetologists from African colubrid bites changed that assessment, and recent events reveal that several other species of rear-fanged snakes have venoms that are potentially lethal to large vertebrates.
Boomslang and vine snake venom are toxic to blood cells and thin the blood (hemotoxic, hemorrhagic). Early symptoms include headaches, nausea, diarrhea, lethargy, mental disorientation, bruising and bleeding at the site and all body openings. Exsanguination is the main cause of death from such a bite.
The Groen Boomslang's venom is the most potent of all rear-fanged snakes in the world based on LD50. Although its venom may be more potent that some vipers and elapids, it causes fewer fatalities owing to various factors(for example,the fangs effectiveness is not high compared with many other snakes;the venom dose delivered is low; and it is generally less aggressive in comparison to other venomous snakes such as cobras and mambas).
Symptoms of a bite from these snakes are nausea and internal bleeding, and one could die from a brain hemorrhage and respiratory collapse.
Experiments made with the secretion of the parotid gland of Tropidonotus and Zamenis have shown that even aglyphous snakes are not entirely devoid of venom, and point to the conclusion that the physiological difference between so-called harmless and venomous snakes is only one of degree, just as there are various steps in the transformation of an ordinary parotid gland into a venom gland or of a solid tooth into a tubular or grooved fang.
The question whether individual snakes are immune to their own venom is not yet definitely settled, though there is a known example of a cobra which self-envenomated, resulting in a large abscess requiring surgical intervention but showing none of the other effects that would have proven rapidly lethal in prey species or humans.[11] Accessed 2 April 2009. Furthermore, certain harmless species, such as the North American Coronella getula and the Brazilian Rhacidelus brazili, are proof against the venom of the crotalines which frequent the same districts, and which they are able to overpower and feed upon. The Tropical Rat Snake, Spilotes variabilis, is the enemy of the Fer-de-lance in St. Lucia, and it is said that in their encounters the Cribo is invariably the victor. Repeated experiments have shown the European Common Snake, Tropidonotus natrix, not to be affected by the bite of Vipera berus and Vipera aspis, this being due to the presence, in the blood of the harmless snake, of toxic principles secreted by the parotid and labial glands, and analogous to those of the venom of these vipers. Several North American species of Rat snakes as well as King snakes have proven to be immune or highly resistant to the venom of Rattle snake species.
The Hedgehog, the Mongoose, the Honey Badger, the Secretary Bird and a few other birds feeding on snakes, are known to be immune to a dose of snake venom; whether the pig may be considered so is still uncertain, although it is well known that, owing to its subcutaneous layer of fat, it is often bitten without ill effect. The garden dormouse (Eliomys quercinus) has recently been added to the list of animals refractory to viper venom. Some populations of California Ground Squirrel are at least partially immune to Rattlesnake venom as adults.
The acquisition of human immunity against snake venom is one of the oldest forms of vaccinology known to date (about AD 60, Psylli Tribe). Since then, many humans have attempted to inoculate themselves with snake venom in order to achieve immunity. Charles Tanner and Herschel Flowers studied with dried snake venom and achieved strong immunity. Joel La Rocque self-injected Eastern diamondback venom and developed a high IgG neutralizing antibody for several rattlesnake species. Harold Mierkey has done so for years.
Tim Friede has studied twice with a self-directed vaccine experiment using pure venom and achieved very high IgG neutralizing antibodies with mamba and cobra venom. The present goal is to develop a DNA-based vaccine for the Eastern Hemisphere using the genes that encode the venom with an electroporation device for DNA delivery. If successful, some of the people that die each year from snakebite in the Eastern Hemisphere will be saved.
The subject of snake venoms is one which has always attracted much attention and which has made great progress within the last quarter of a century. Plants used to treat snakebites in Trinidad and Tobago are made into tinctures with alcohol or olive oil and kept in rum flasks called 'snake bottles'. Snakes bottles contain several different plants and/ or insects. The plants used include the vine called monkey ladder (Bauhinia cumanensis or Bauhinia excisa, Fabaceae) is pounded and put on the bite. Alternatively a tincture is made with a piece of the vine and kept in a snake bottle. Other plants used include: mat root (Aristolochia rugosa), cat's claw (Pithocellobium unguis-cati), tobacco (Nicotiana tabacum), snake bush (Barleria lupulina), obie seed (Cola nitida), and wild gri gri root (Acrocomia ierensis). Some snake bottles also contain the caterpillars (Battus polydamus, Papilionidae) that eat tree leaves (Aristolochia trilobata). Emergency snake medicines are obtained by chewing a three-inch piece of the root of bois canôt (Cecropia peltata) and administering this chewed-root solution to the bitten(usually hunting dogs). This is a common native plant of Latin America and the Caribbean which makes it appropriate as an emergency remedy. Another native plant used is mardi gras (Renealmia alpinia)(berries), which are crushed together with the juice of wild cane (Costus scaber) and given to the bitten. Quick fixes have included applying chewed tobacco from cigarettes, cigars or pipes as well. Making cuts around the puncture or sucking out the venom has also been helpful.
Especially noteworthy is progress regarding the defensive reaction by which the blood may be rendered proof against their effect, by processes similar to vaccination—antipoisonous serotherapy.
The studies to which we allude have not only conduced to a method of treatment against snake-bites, but have thrown a new light on the great problem of immunity.
They have shown that the antitoxic sera do not act as chemical antidotes in destroying the venom, but as physiological antidotes; that, in addition to the venom glands, snakes possess other glands supplying their blood with substances antagonistic to the venom, such as also exist in various animals refractory to snake venom, the hedgehog and the mongoose for instance.
Unfortunately, the specificity of the different snake venoms is such that, even when the physiological action appears identical, serum injections or graduated direct inoculations confer immunity towards one species or a few allied species only.
Thus, a European in Australia who had become immune to the venom of the deadly Australian Tiger Snake, Notechis scutatus, manipulating these snakes with impunity, and was under the impression that his immunity extended also to other species, when bitten by a Denisonia superba, an allied elapine, died the following day.
In India, the serum prepared with the venom of Naja tripudians has been found to be without effect on the venom of the two species of kraits of the genus Bungarus, and the Old World vipers Daboia russelli and Echis carinatus, and the pit viper Trimeresurus popeiorum. Daboia russelli serum is without effect on colubrine venoms, or those of Echis and Trimeresurus.
In Brazil, serum prepared with the venom of the New World pit viper Lachesis lanceolatus is without action on Crotalus venom.
Antivenom snakebite treatment must be matched as the type of envenomation that has occurred.
In the Americas, polyvalent antivenoms are available that are effective against the bites of most pit vipers.
These are not effective against coral snake envenomation, which requires a specific antivenom to their neurotoxic venom.
The situation is even more complex in countries like India, with its rich mix of vipers (family Viperidae) and highly neurotoxic cobras and kraits of the family Elapidae.
This article is based on the 1913 book The Snakes of Europe, by G. A. Boulenger, which is now in the public domain in the United States (and possibly elsewhere) because of its age. Because of its age, the text in this article should not necessarily be viewed as reflecting the current knowledge of snake venom.
|
||||||||||||||||||||||||||||||||||||||||||||||||||