Saxitoxin ( STX) is a potent neurotoxin and the best-known paralytic shellfish toxin. Ingestion of saxitoxin by humans, usually by consumption of shellfish contaminated by toxic , is responsible for the illness known as paralytic shellfish poisoning (PSP).
The term saxitoxin originates from the genus name of the butter clam ( Saxidomus) from which it was first isolated. But the term saxitoxin can also refer to the entire suite of more than 50 structurally related neurotoxins (known collectively as "saxitoxins") produced by Protist, algae and cyanobacteria which includes saxitoxin itself (STX), neosaxitoxin (NSTX), (GTX) and decarbamoylsaxitoxin (dcSTX).
Saxitoxin has a large environmental and economic impact, as its presence in Bivalvia shellfish such as mussels, clams, oysters and scallops frequently leads to bans on commercial and recreational shellfish harvesting in many temperate coastal waters around the world including the Northeastern and Western United States, Western Europe, East Asia, Australia, New Zealand, and South Africa. In the United States, paralytic shellfish poisoning has occurred in California, Oregon, Washington, Alaska, and New England.
Saxitoxin has also been found in at least twelve marine puffer fish species in Asia and one freshwater fish tilapia in Brazil. The ultimate source of STX is often still uncertain. The dinoflagellate Pyrodinium bahamense is the source of STX found in Florida. Recent research shows the detection of STX in the skin, muscle, viscera, and gonads of "Indian River Lagoon" southern puffer fish, with the highest concentration (22,104 μg STX eq/100 g tissue) measured in the ovaries. Even after a year of captivity, Landsberg et al. found the skin mucus remained highly toxic. The concentrations in puffer fish from the United States are similar to those found in the Philippines, Thailand, Japan, and South American countries. Puffer fish also accumulate a structurally distinct toxin, tetrodotoxin.For a more comprehensive discussion of TTX-producing bacterial species associated with metazoans from which the toxin has been isolated or toxicity observed, and biosynthesis, see
Several Total synthesis of saxitoxin have been accomplished.
The voltage-gated sodium channel is essential for normal neuronal functioning. It exists as integral membrane proteins interspersed along the axon of a neuron and possessing four Protein domain that span the cell membrane. Opening of the voltage-gated sodium channel occurs when there is a change in voltage or some ligand binds in the right way. It is of foremost importance for these sodium channels to function properly, as they are essential for the propagation of an action potential. Without this ability, the nerve cell becomes unable to transmit signals and the region of the body that it enervates is cut off from the nervous system. This may lead to paralysis of the affected region, as in the case of saxitoxin.
Saxitoxin binds reversibly to the sodium channel. It binds directly in the pore of the channel protein, occluding the opening, and preventing the flow of sodium ions through the membrane. This leads to the nervous shutdown described above.
Saxitoxin biosynthesis is the first non-terpene alkaloid pathway described for bacteria, though the exact mechanism of saxitoxin biosynthesis is still essentially a theoretical model. The precise mechanism of how substrates bind to is still unknown, and genes involved in the biosynthesis of saxitoxin are either putative or have only recently been identified.
Two biosyntheses have been proposed in the past. Earlier versions differ from a more recent proposal by Kellmann, et al. based on both biosynthetic considerations as well as genetic evidence not available at the time of the first proposal. The more recent model describes a STX gene cluster (Sxt) used to obtain a more favorable reaction. The most recent reaction sequence of Sxt in cyanobacteria is as follows. Refer to the diagram for a detailed biosynthesis and intermediate structures.
The medical and environmental importance of saxitoxin derives from the consumption of contaminated shellfish and certain finfish which can concentrate the toxin from dinoflagellates or cyanobacteria. The blocking of neuronal which occurs in PSP produces a flaccid paralysis that leaves its victim calm and conscious through the progression of . Death often occurs from respiratory failure. PSP toxins have been implicated in various marine animal mortalities involving food chain of the toxin from its algal source up the food chain to higher .
Studies in animals have shown that the lethal effects of saxitoxin can be reversed with 4-aminopyridine, but there are no studies on human subjects. As with any paralytic agent, where the acute concern is respiratory failure, mouth-to-mouth resuscitation or artificial ventilation of any means will keep a poisoned victim alive until antidote is administered or the poison wears off.
After the 1969 ban on biological warfare by President Nixon, the US stockpiles of saxitoxin were destroyed, and development of saxitoxin as a military weapon ceased. In 1975, the CIA reported to Congress that it had kept a small amount of saxitoxin and cobra venom against Nixon's orders which was then destroyed or distributed to researchers.
It is listed in schedule 1 of the Chemical Weapons Convention. The United States military isolated saxitoxin and assigned it the chemical weapon designation TZ.
|
|