|Molar mass||299.29 g·mol−1|
Except where noted otherwise, data is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
|what is: / ?)(|
Saxitoxin (STX) is the best-known paralytic shellﬁsh toxin (PST), although other related compounds have been reported, such as neosaxitoxin (NSTX), the 11-alpha and 11-beta-O-sulphates of saxitoxin and neosaxitoxin, and carbonyl-N-sulphate derivatives of saxitoxin and neosaxitoxin.
STX is a neurotoxin naturally produced by certain species of marine dinoflagellates (Alexandrium sp., Gymnodinium sp., Pyrodinium sp.) and cyanobacteria (Anabaena sp., some Aphanizomenon spp., Cylindrospermopsis sp., Lyngbya sp., Planktothrix sp.). Ingestion of saxitoxin (usually through shellfish contaminated by toxic algal blooms) is responsible for the human illness known as paralytic shellfish poisoning (PSP).
In fact, the term saxitoxin originates from the species name of the butter clam (Saxidomus giganteus) in which it was first recognized. But, the term saxitoxin can also refer to the entire suite of related neurotoxins (known collectively as "saxitoxins") produced by these microorganisms, which include pure saxitoxin (STX), neosaxitoxin (NSTX), gonyautoxins (GTX) and decarbamoylsaxitoxin (dcSTX).
Detection of saxitoxin in shellfish such as mussels, clams and scallops frequently leads to closures of commercial and recreational shellfish harvesting, especially in California, Oregon, Washington, and New England.
STX has been found in at least 12 marine puffer fish fish species in Asia and one freshwater fish tilapia in Brazil. However, the ultimate source of STX is still uncertain. In the United States, paralytic shellfish poisoning is limited to New England and the West Coast. 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, the skin mucus remained highly toxic. The various concentrations in puffer fish from the United States are similar to those found in the Philippines, Thailand, Japan, and South American countries.
Saxitoxin is a neurotoxin that acts as a selective sodium channel blocker. One of the most potent natural toxins known to man, it acts on the voltage-gated sodium channels of nerve cells, preventing normal cellular function and leading to paralysis.
Although STX biosynthesis seems complex, organisms from the two kingdoms, species of marine dinoflagellates and freshwater cyanobacteria, are capable of making these toxins by the same biosynthetic pathway. The enzymes involved in the biosynthesis of STX have not been identified by previous studies.
Saxitoxin synthesis is the first non-terpene alkaloid pathway described for bacteria. A complete STX biosynthetic gene cluster (sxt) is used to obtain a more favourable reaction. The predicted reaction sequence of suggested SxtA, based on its primary structure, is the loading of the ACP with acetate from acetyl-CoA, followed by SxtA-catalyzed methylation of acetyl-ACP, which is then converted to propionyl-ACP. Later another SxtA performs a Claisen condensation reaction between propionyl-ACP and arginine producing 4.
SxtG transfers an amidino group from arginine to the α-amino 4 group producing 5, which later undergoes retroaldol-like condensation by SxtB. SxtD adds a double bond between C-1 and C-5 of 6, which gives rise to the 1,2-H shift between C-5 and C-6 in 7. SxtS performs an epoxidation of the double bond and opening of the epoxide to an aldehyde. SxtU reduces the terminal aldehyde group of the STX precursor 9 forming 10. SxtI catalyzes the transfer of a carbamoyl group to the free hydroxyl group on 10. SxtH and SxtT perform a similar function which is the consecutive hydroxylation of C-12 terminating the STX biosynthetic pathway. This is only a proposed biosynthetic pathway; the actual mechanism of how substrates bind to the enzymes is still unknown.
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The challenges that face the chemical synthesis of this natural product include the dense arrangement of heteroatoms, the tricyclic structure, and the dicationic nature of final STX product (that complicates its purification). The starting material for one synthesis of this compound begins with a commercially available compound, a glycerol-derived sulfamate ester.[non-primary source needed] This is taken through a complex series of steps that include protections/deprotections, carbon-carbon bond forming, and functional group modification steps, to create an intermediary heterocycle, a oxathiazinane; its hydrolysis gives the tricyclic structure seen on the final product, STX, that has all of the required carbon atoms and carbon-carbon bonds. After the remainder of the mult-step process,[clarification needed] the final STX product was available (in the case of this one example) at an overall yield of 1.3%.[non-primary source needed]
The human illness associated with ingestion of harmful levels of saxitoxin is known as paralytic shellfish poisoning, or PSP, and saxitoxin and its derivatives are often referred to as "PSP toxins".
The medical and ecological importance of saxitoxin lies mainly in effects of harmful algal blooms on shellfish and certain finfish which can concentrate the toxin, making it available both for human consumption as well as by various marine organisms. The blocking of neuronal sodium channels which occurs in PSP produces a flaccid paralysis that leaves its victim calm and conscious through the progression of symptoms. Death often occurs from respiratory failure. PSP toxins have been implicated in various marine animal mortalities involving trophic transfer of the toxin from its algal source up the food web to higher predators.
STX is highly toxic, killing guinea pigs at only 5 µg/kg when injected i.m. The lethal doses for mice are very similar with varying administration routes: t i.p. (LD50 = 10 µg/kg), i.v. (LD50 = 3.4 µg/kg) or p.o. (LD50 = 263 µg/kg). The oral LD50 for humans is 5.7 µg/kg, therefore approximately 0.57 mg of saxitoxin is lethal if ingested and the lethal dose by injection is about ten times lower (approximately 0.0000006 g). The human inhalation toxicity of aerosolized saxitoxin is estimated to be 5 mg·min/m³. Saxitoxin can enter the body via open wounds and a lethal dose of 0.05 mg/person by this route has been suggested. Saxitoxin is 1,000 times more toxic than the potent nerve gas sarin.
- 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.
- U-2 pilot Francis Gary Powers was issued a hollow silver dollar containing a tiny, saxitoxin-impregnated needle, to be used to commit suicide in case of capture by enemy forces.
- Though its early isolation and characterization were from military efforts, saxitoxin has been important to cellular research in delineating the function of the sodium channel.
- Canadian Reference Materials
- Action potential
- Alexandrium tamarense sp.
- Anabaena circinalis
- Harmful algal bloom
- Paralytic shellfish poisoning
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