Puffer fish toxin

Lastly, tetrodotoxin, the Japanese puffer fish toxin, is a polyhydroxylated reduced 2-aminoquinazoline derivative that has attracted a lot of interest, and a number of asymmetric total syntheses have recently been published <2003JA8798, 2003JAl 1510, 2004AGE4782, 2005CRV4537>. 

Chemicals, which affect neurons, such as the Puffer fish toxin tetrodotoxin, which blocks voltage-gated Na+ channels in motor neurons, will also affect other cells such as skeletal muscle cells, causing paralysis. 

Saxitoxin is a naturally occurring toxin that is synthesized by various marine dinoflagellates. It is used in neurochemical and molecular biology research. Saxitoxin causes paralytic shellfish poisoning. It is far more potent than the classic puffer fish toxin, tetrodotoxin. Saxitoxin is one of only two naturally occurring schedule 1 chemical warfare agents (the other is ricin). 

The puffer fish toxin. Captain Cook severely affected in 1774. The fish is prepared by trained cooks and eaten as fugu in Japan. Also found in ovaries and liver of related fish species and some cephalopods. Non-protein MW 319. Effects numbness and tingling of lips, vomiting, fall in BP, weakness, paralysis, respiratory failure, death. Lethal dose in mice 5 pg/kg among the most potent of toxins. Blocks sodium channels and prevents depolarization. Believed to be produced by bacteria in the fish. Looked at by Japan in WWII as a potential CW agent. 

T. Nishikawa, D. Urabe, K. Yoshida, T. Iwabushi, M. Asai, andM. Isobe, Stereocontrolled synthesis of 8,11-dideoxytetrodotoxin, unnatural analogue of puffer fish toxin, Org. Lett., 4 (2002) 2679-2682. 

Toxins that bind to sodium channels and promote sodium flux. Examples of these include tetrodotoxin (puffer fish toxin), and scorpion venom. 

Yotsu-Yamashita, M. 2001. Chemistry of puffer fish toxin. J. Toxicol-Toxin Rev. 20, 51-66. 

The first asymmetric total synthesis of tetrodotoxin, a puffer fish toxin ... 

Naturally occurring lipid-soluble molecules that are able to transport ions across cell membranes are called ionophores (ion carriers, Greek c )6p(0, phew, to carry), and they play numerous critical roles in biology. They encase metal ions in a mainly hydrocarbon shell, and this allows them to pass through lipid membranes. Sometimes, as with the puffer fish toxin, tetrodotoxin, 4.28, this means that they are very toxic, as they upset the normal ion balance within cells. In other cases, as with amphotericin B, 4.29, there is a medicinal use although it is quite toxic, it can be used in low doses to treat the protozoan infection leishmaniasis. 

With respect to toxins which target specific sites, insight can be obtained from the anomolies that are observed. For example, both puffer fish and tetrodotoxin-containing crabs (96) are insensitive to tetrodotoxin. The investigation of such insensitivities can provide information about membrane channels and their toxin binding sites. 

Among the marine toxins relevant for human intoxication, tetrodotoxin (TTX) has been known as one of the most potent low-molecular weight neurotoxins. Puffer fish (family Tetraodontidae — the source of the TTX name) were originally thought to be the only animal from which TTX could be isolated. Subsequent works determined that TTX also exists in a large number of other marine organisms of different phylogenic classes e.g. 

A mouse bioassay method is useful for screening of the toxicity of various organisms from affected areas, although this method may not be sufficient for the identification of the toxin. Recently, distribution of tetrodotoxin in the marine ecosystem has expanded from puffer-fishes to some other animals. Rapid and accurate determination of the toxin occurring in those organisms is becoming increasingly important from the public health standpoint. 

A variety of toxins that modulate voltage-gated sodium channels have been used to probe channel function. They can be classified on the basis of five discrete binding sites (Table 1). These binding sites are commonly found on all a-subunits and are being characterized at the molecular level. The sensitivity to the puffer fish poison tetrodotoxin (TTX) has been used to subdivide voltage-gated sodium channels (Table 3). 

Many fish species, over 700 species worldwide, are either directly toxic or upon ingestion are poisonous to humans. A classic example is the toxin produced by the puffer fishes (Sphaeroides spp.) called tetrodotoxin (TTX). Tetrodotoxin is concentrated in the gonads, liver, intestine, and skin, and poisonings occurs most frequently in Japan and other Asian countries where the flesh, considered a delicacy, is eaten as fugu. Death occurs within 5 to 30 minutes and the fatality rate is about 60%. TTX is an inhibitor of the voltage-sensitive Na channel (like saxitoxin) it may also be found in some salamanders and may be bacterial in origin. 

Interspecific differences are also known for some naturally occurring poisons. Nicotine, for instance, is used as an insecticide and kills many insect pests at low doses, yet tobacco leaves constitute a normal diet for several species. As indicated earlier, most strains of rabbit eat Belladonna leaves without ill effects, whereas other mammals are easily poisoned. Natural tolerance to cyanide poisoning in millipedes and the high resistance to the powerful axonal blocking tetrodotoxin in puffer fish are examples of the tolerance of animals to the toxins they produce. 

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