The Chemistry of Spider venom

This article was originally posted at The Chemistry of Spider venom
Spider venoms can be grouped into two broad categories: necrotic, and neurotoxic. Necrotic, or cytotoxic venoms, are those which cause cell and tissue damage after envenomation. This can lead to the appearance of inflammation, lesions, and blisters. Neurotoxic venoms, on the other hand, exert their effects on the nervous system, and interfere with signalling between neurons. In extreme cases, these can lead to respiratory and cardiac arrest. Note that some spider venoms can actually contain both necrotic and neurotoxic components.

Components of the venom are often grouped into categories according to their molecular weights: low molecular weight compounds (<1000), peptides (1000-10000), & proteins (10000+). For different species of spider, a different one of these categories may contain the primary toxic component of the venom. Inspite of the huge number of different spider species, a comparatively small percentage of spider venoms have had their compositions characterised. Generally, however, they contain a large number of compounds from all three groups.

The low molecular weight compounds consist of salts, carbohydrates, and small organic compounds such as amines, acids, and acylpolyamines. It’s thought that, the potassium ions in salts may assist the toxic portions of the venom in reaching their molecular targets in victims. High potassium ion concentrations can also affect the signalling between neurons in the nervous systems of insects. Amines, meanwhile, can include neurotransmitters such as serotonin and noradrenaline. These are similarly capable of interacting with an insect’s nervous system, and also aid in the spreading of the venom through the insects body.

Acylpolyamines are significant low molecular weight toxins in the venoms of some spiders, and more than 100 have now been characterised. Often, spider venoms will contain a number of different acylpolyamines, rather than just one. It’s thought that their primary purpose in venoms is to paralyse insects by blocking glutamate receptors.

Peptides are the main component in most spider venoms. On average, they’re thought to contain around 25% polypeptides by weight, and analysis has suggested that some individual venoms could harbour up to 1000 different peptides. Some contain linear, cytolytic peptides which have necrotic effects. The action of these cytolytic peptides is relatively non-specific, and they can also act synergistically with neurotoxic components. It’s also been suggested that they could aid in the external digestion of the spider’s prey.

It’s disulfide-containing peptides that are the major players in spider venoms, however. Aside from a few exceptions, in most venoms they are the major toxic component. They are more potent than the cytolytic peptides, and are also more selective in terms of their targets. These tend to be ion channels on neurons. It’s also been suggested, due to the nature of some other targets of these compounds, that some of them may have been evolved to ward off predators, rather than for insecticidal activity.

Finally, the higher molecular weight components include enzymes and larger proteins. Enzymes have an obvious role in external digestion of the spider’s prey once it’s been envenomated, and a variety of different enzymes have been identified in spider venom. Additionally, by breaking down extracellular structures, they also enable the spread of the venom. One enzyme, hyaluronidase, is also thought to be for the purpose of self-defence, as its target, hyaluronan, is found in vertebrates but not invertebrates..

High molecular weight proteins are fairly uncommon as toxic components of the venom. However, there is a notable exception: that of Widow spiders, which include the Black Widow Spider. Their venom contains toxins called latrotoxins, which have been the subject of many studies. One such toxin, alpha-latrotoxin, binds to nerve terminals and causes huge release of neurotransmitters into synapses, blocking signal transmission. The effects of a Black Widow spider bite can last up to 5 days, though they rarely kill.

You might wonder why scientists have spent so much time researching spider venoms, other than just out of curiosity. The demand for better insecticides, which are capable of exerting effects on specific insects without having any detrimental effects on other wildlife, means that we are looking to spider venoms as a potential source of insecticidal compounds. More widely, their chemical diversity also makes them candidates for drug discovery programs.

As mentioned at the outset, the venom of the majority of spiders is largely harmless to humans. There are, though, a few notable exceptions. Widow, Recluse, Wandering, and Funnel-Web spiders are all considered to pose a threat to human health.