Chemistry of Venoms
What do animal venoms contain? Animal venoms are mixtures of 20 to 25 different kinds of molecules dissolved in water. Most frequently, venomous species have proteins or smaller polypeptides ranging from 30 to 80 amino acid residues. The poisonous species primarily have alkaloids, which are small molecules that have very strong biological effects.
 | | Zoltan Takacs | | Scorpions are examples of venomous animals who use their venom for defense and immobilizing prey. |
Acetylcholine receptors, potassium channels, calcium channels--these are different receptors on the surface of the nerve or muscle cells that have a very basic role in maintaining and propagating action potential and muscle contraction. And because one of the primary functions of animal venoms is to immobilize the prey or the predator, toxins are targeted against those molecules that play a very basic role in the locomotion of the prey animal.
Many animal toxins are targeted against the acetylcholine receptor because of its function, and it is found everywhere in the animal kingdom. There are some toxins, for example, dendrotoxins and some bungarotoxins, that also attack the neuromuscular junction, but they're not acting on the muscle cell. They're acting by inhibiting acetylcholine release from the nerve terminal or they're causing abnormally high release from the nerve terminal. The release of so much acetylcholine, which also leads to a neuromuscular blockage, will clinically lead to a failure of respiration and therefore lead to the death of the victim.
Venomous and poisonous species in very different taxa have toxins with very similar actions that compose these poisons and venoms. For example, toxins that act on the very same acetylcholine receptor of animals have been isolated from corals, cone shells, sea snakes and cobras. Similarly, toxins interfering with the normal operation of nerve cells by acting on potassium channels have been isolated from scorpions, bees and mambas. The important message here is that all animal venoms, regardless of which group produces it, are targeted against key elements of locomotion because they have to immobilize the predator or prey animal in order to be an evolutionary success.
The sodium channel is a big protein in the membrane of the nerve and muscle cells, and it makes an excellent target for different toxins, such as scorpion toxins, anemone toxins and amphibian toxins. While different kinds of poison arrow frogs, newts from California and birds from Papua New Guinea--there are three species of poisonous birds--have tetrodotoxin and homobatrachotoxin in their bodies, all of these toxins bind to specific regions of the same sodium channel. Batrachotoxin, which is not a polypeptide and can therefore go through the lipid bilayer, binds more in the core part of that sodium channel. Then there is beta-scorpion toxin, which is a big polypeptide that binds to the surface of the sodium channel.
What does this mean pharmacologically? A current can be detected when potassium ions go through a potassium channel, and since many of these channels are targets for animal venoms, they can be blocked. With dendrotoxin, for example, which is a toxin isolated from the elapid mamba snake, a relative of the cobra, you can see a reduction of the current experimentally as you start to increase the toxin concentration. This is what happens when an animal gets bitten by a venomous snake. The ion channels get blocked, and that may lead to respiratory paralysis.
Venoms as enzymes
Toxins attack the nerve and muscle cells, but enzymes are another important component in animal venoms. Enzymes don't exist in the venom of all animals, only in venomous species. The poisonous species normally don't have enzymes, because enzymes have a digestive function. The venom gland of snakes, for example, is a modified salivary gland, so it still retains its digestive function, and that's why you find so many enzymes in snake venoms.
Enzymes are found in all snake venoms, and many of these enzymes are also found in other animal venoms. Some enzymes are found only in the venoms of vipers and pit vipers, while others are found only in the venom of elapids, such as cobras and sea snakes. Some specific enzymes are unique for particular groups of species. If you follow the enzyme nomenclature, you realize they break down tissues; they are mostly proteinases, nucleases, phospholipases--they "chew up," or digest, the proteins of the prey animal.
This can be shown in molecular terms.  | |
| Knowledge Test | | | Now that you have completed this free seminar, see what you have learned by answering a few short questions on "The Biology of Venomous Animals." | | |
Crotalase, a snake venom enzyme that is isolated from a North American rattlesnake, acts on fibrinogen. Fibrinogen is a molecule in the blood that is needed for coagulation. In normal physiological conditions, thrombin slices off fibrinopeptides A and B and the remaining monomer is able to polymerize, and through other steps will cause the blood to clot. So what does snake venom do? Once crotalase, in the snake venom, gets into the circulation of an animal, it splits off only fibrin peptide A and results in a monomer that is unable to polymerize. So the animal who has been bitten by that snake will have internal bleeding, because all of the fibrinogens will be consumed by the crotalase and will be unable to form the polymer that lets the blood clot. |
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