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 algal blooms, 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 protists, algae and cyanobacteria which includes saxitoxin itself (STX), neosaxitoxin (NSTX), gonyautoxins (GTX) and decarbamoylsaxitoxin (dcSTX).

Saxitoxin has a large environmental and economic impact, as its presence in bivalve 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.

Source in nature

Saxitoxin is a neurotoxin naturally produced by certain species of marine dinoflagellates (Alexandrium sp., Gymnodinium sp., Pyrodinium sp.) and freshwater cyanobacteria (Dolichospermum cicinale sp., some Aphanizomenon spp., Cylindrospermopsis sp., Lyngbya sp., Planktothrix sp.) Saxitoxin accumulates in "planktivorous invertebrates, including mollusks (bivalves and gastropods), crustaceans, and echinoderms".

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, and South American countries. Puffer fish also accumulate a structurally distinct toxin, tetrodotoxin.

Structure and synthesis

Saxitoxin dihydrochloride is an amorphous hygroscopic solid, but X-ray crystallography of crystalline derivatives enabled the structure of saxitoxin to be determined. Oxidation of saxitoxin generates a highly fluorescent purine derivative which has been utilized to detect its presence.

Several total syntheses of saxitoxin have been accomplished.

Mechanism of action

thumb|A diagram of the membrane topology of a voltage gated sodium channel protein. Binding sites for different neurotoxins are indicated by color. Saxitoxin is denoted by red.

Saxitoxin is a neurotoxin that acts as a selective, reversible, voltage-gated sodium channel blocker. One of the most potent known natural toxins, it acts on the voltage-gated sodium channels of neurons, preventing normal cellular function and leading to paralysis.

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 enzymes 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

Illness in humans

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". 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.

Military interest

Saxitoxin, by virtue of its extremely low LD<sub>50</sub>, readily lends itself to weaponization. In the past, it was considered for military use by the United States and was developed as a chemical weapon by the US military. It is known that saxitoxin was developed for both overt military use as well as for covert purposes by the CIA. Among weapons stockpiles were M1 munitions that contained either saxitoxin, botulinum toxin or a mixture of both. The CIA is known to have issued a small dose of saxitoxin to U-2 spy plane pilot Francis Gary Powers in the form of a small injection hidden within a silver dollar, for use in the event of his capture and detainment. 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.

See also

References

  • [http://www.uaf.edu/seagrant/issues/PSP/PSP.pdf] Paralytic Shellfish Poisoning
  • [http://www.chm.bris.ac.uk/motm/stx/saxi.htm] Neil Edwards. The Chemical Laboratories. School of Chemistry, Physics & Environmental Science. University of Sussex at Brighton. Saxitoxin - from food poisoning to chemical warfare
  • Toxic cyanobacteria in water: A guide to their public health consequences, monitoring and management. Edited by Ingrid Chorus and Jamie Bartram, 1999. Published by World Health Organization.