1 ANIMAL TOXINS (SNAILS) Cuyno, Joanna Marie Torno, Mylene III- BSCT Cuyno, Joanna Marie Torno, Mylene III- BSCT

2 Overview General Information on Snails Conus Snails Conotoxins Nature, Symptoms, Types  α- conotoxin, δ- conotoxin, κ- conotoxin, μ- conotoxin, ω- conotoxin, conantoxins

3 Snails are one of the earliest known type of animals in the world. They are able to adapt to a variety of living conditions and they don’t require large amounts of food. As the snail moves, it leaves behind a trail a slime. This allows it to easily move across any type of terrain without injuring its body. They aren’t able to hear at all so they rely on their sense of touch to interact with each other.

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5 There are mainly 600 species of cone snails. The shells of Conus species vary in size. The shells are shaped more or less like the geometric shape known as a cone, as one might expect from the popular and scientific name. Cone snails are carnivorous, and predatory. They hunt and eat prey such as marine worms, small fish, mollusks, and even other cone snails.

6 The osphradium (a chemoreceptory organ) in the family Conidae is more highly specialized than the same organ in any other family of gastropods. It is through this sensory modality that cone snails become aware of the presence of a prey animal, not through vision. The osphradium (a chemoreceptory organ) in the family Conidae is more highly specialized than the same organ in any other family of gastropods. It is through this sensory modality that cone snails become aware of the presence of a prey animal, not through vision. Cone snails use a radula tooth as a harpoon-like structure for predation. Each of these harpoons is a modified tooth, primarily made of chitin and formed inside the mouth of the snail, in a structure known as the radula. Cone snails use a radula tooth as a harpoon-like structure for predation. Each of these harpoons is a modified tooth, primarily made of chitin and formed inside the mouth of the snail, in a structure known as the radula.

7 The conotoxins are paralytic poisons from Pacific cone snails that block the transmission of a nerve impulse from the nerve to the muscle at the neuromuscular junction. These are short peptides of amino acids held in very tight conformations by multiple disulfide bridges.

8 Conus peptide toxins are categorized into three different cabalic modes of action depending on snail species and their prey. Lightening strike cabal- Excitotoxic shock: a rapid activation of Na ion channels causing a tetanic response resulting in a tonic/clonic paralysis. Motor cabal - Neuromuscular paralysis: neurotoxin bind and block Na ion channels to acetylcholine resulting in flaccid paralysis. Nirvana cabal - the sleeper and sluggish peptides that quiets down neuronal circuitry resulting in paralysis.

9 There are 6types of conotoxins (so far), namely: αα- conotoxin  δ δ- conotoxin  κ κ- conotoxin  μ μ- conotoxin  ω ω- conotoxin  conantokins

10 Intense, localized pain, swelling, numbness and tingling and vomiting. Severe cases involve muscle paralysis, changes in vision and respiratory failure that can lead to death. There is no antivenom, and treatment involves providing life support until the venom is metabolised by the victim.

11 She is Dr. Lourdes Jansuy Cruz, 67, a National Scientist based at the University of the Philippines- Diliman, was recognized for her role in discovering Conotoxins (or toxins from marine snails) during the 1970s to 80s.

12 CONOTOXINS

13 α -conotoxin α -conotoxin inhibits nicotinic acetylcholine receptors at nerves and muscles. The α -conotoxins are antagonists of ACh binding, and, being competitive inhibitors, they bind in the same region as ACh and prevent the channel from opening. These alpha conotoxins cause postsynaptic inhibition at the neuromuscular junction resulting in paralysis and death.

14 α -conotoxin Alpha conotoxins have two types of cysteine arrangements: The α- conotoxins GI, GIA, and GII (from Conus geographus ) and MI (from Conus magus) are homologous peptides of 13 and 15 amino acids respectively. Another goup of α- conotoxins have their two disulphide bridges linked in 4:7 loop configuration.

15 μ -conotoxin μ -conotoxin are hydroxyproline- rich basic peptides of 22 amino acids. μ -conotoxin act upon sodium channels in muscle, and also, to a very limited extent, in neurons, where they bind to a site designated 'binding site one' at the mouth of the sodium channel, and there by inhibit the influx of sodium into the cell which renders the organism paralysed.

16 ω -conotoxin

17 δ -Conotoxins

18 κ -conotoxin, a 27-amino acid toxin from Conus purpurascens venom inhibits the Shaker potassium channel, and has been chemically synthesized in a biologically active form. The disulfide connectivity of the peptide was determined.

19 The conantokins are considered to be part of the “nirvana cabal” whose major function is to deaden the sensory circuitry of the prey, facilitating prey capture by fish- hunting cone snails using the net strategy. A notable biochemical feature of conantokins is the presence of multiple residues of post- translationally modified amino acid, γ - carboxyglutamate (Gla), which are essential for their biological activities. They are the only naturally-derived peptides to do so. The conantokins [28] selectively inhibit a subtype of glutamate receptor, the NMDA (N-methyl- Daspartate) receptors, which are ligand-gated Ca 2+ channels involved in seizures in intractable epilepsy.

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