Tetrodotoxin is well known as the toxic principle in the puffer fish (Tetraodon species), regarded as delicacy in Japanese cuisine. As potent sodium channel blockers, both saxitoxin and tetrodotoxin are valuable pharmacological tools.
Saxitoxin (Figure 136) was first isolated from the Alaskan butter clam (Saxidomus giganteus) but has since been found in many species of shellfish, especially bivalves such as mussels, scallops, and oysters. These filter feeders consume dinoflagellates (plankton) and can accumulate toxins synthesized by these organisms, particularly during outbreaks known as red tides, when conditions favour formation of huge blooms of the dinoflagellates. Species of the dinoflagellate Gonyaulax in marine locations, or the cyanobacterium Aphanizomenon in freshwater, have been identified among the causative organisms, and the problem is encountered widely in temperate and tropical areas (including Europe, North America, and Japan). Commercial production of shellfish is routinely monitored for toxicity, which will slowly diminish as conditions change and the causative organism disappears from the water. About a dozen natural saxitoxin-related structures have been characterized, and mixtures in various proportions are typically synthesized by a producer, with the possibility that the shellfish may also structurally modify the toxins further. Acute and often fatal poisonings caused by the consumption of contaminated shellfish are termed paralytic shellfish poisoning (PSP), which involves paralysis of the neuromuscular system, death resulting from respiratory failure. Saxitoxin is a cationic molecule, which binds to sodium channels, blocking the influx of sodium ions through excitable nerve membranes, and is a valuable pharmacological tool for the study of this process. Saxitoxin and tetrodotoxin (below) are some of the most potent non-protein neurotoxins known, and are active at very low concentrations (µg kg−1).
Tetrodotoxin (Figure 136) is traditionally associated with the puffer fish, Tetraodon species, a fish known as fugu, a highly prized delicacy eaten in Japan. Preparation of fugu is a skilled operation in which organs containing the highest levels of toxin, e.g. liver, ovaries, and testes, are carefully separated from the flesh. Even so, deaths from fugu poisoning are not uncommon, and the element of risk presumably heightens culinary appreciation of the fish. As with saxitoxin, tetrodotoxin appears to be produced by microorganisms, and symbiotic marine bacteria, e.g. Vibrio species, have been implicated as the synthesizers. In addition to fugu, several other species of fish, newts, and frogs have been found to accumulate tetrodotoxin or related structures. The mode of action of tetrodotoxin is exactly the same as that of saxitoxin above, though there are some subtle differences in the mechanism of binding.
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