Gonyautoxin

Last updated
Gonyautoxin 2
Gonyautoxin 2.svg
Names
IUPAC name
(3aS,4R,9R,10aS)-2,6-Diamino-4-(((aminocarbonyl)oxy)methyl)-3a,4,8,9-tetrahydro-1H,10H-pyrrolo(1,2-c)purine-9,10,10-triol 9-(Hydrogen Sulfate)
Other names
Gonyautoxin 2, GTX-2, GTX-II
Identifiers
ChEBI
ChemSpider
PubChem CID
UNII
Properties
C10H17N7O8S
Molar mass 395.35 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Gonyautoxins (GTX) are a few similar toxic molecules that are naturally produced by algae. They are part of the group of saxitoxins, a large group of neurotoxins along with a molecule that is also referred to as saxitoxin (STX), neosaxitoxin (NSTX) and decarbamoylsaxitoxin (dcSTX). Currently eight molecules are assigned to the group of gonyautoxins, known as gonyautoxin 1 (GTX-1) to gonyautoxin 8 (GTX-8). Ingestion of gonyautoxins through consumption of mollusks contaminated by toxic algae can cause a human illness called paralytic shellfish poisoning (PSP).

Contents

Natural sources

Gonyautoxins are naturally produced by several marine dinoflagellates species ( Alexandrium sp., Gonyaulax sp., Protogonyaulax sp.). [1] [2] The paralytic shellfish poisoning caused by these toxins is connected with dinoflagellate blooms known as “red tides”, even though the coloration of the water isn't a necessity. The threshold concentration of the organisms that are capable to produce the toxins is lower than the lowest visually detectable concentration. [3] Subsequently, the toxins are taken up by shellfish and undergo bioaccumulation.

Structure

As part of the group of saxitoxins, the gonyautoxins have their structure based on the 2,6-diamino-4-methyl-pyrollo[1,2-c]-purin-10-ol skeleton (also known as the Saxitoxin-gonyautoxin skeleton). [2] The different molecules only differ from each other by their substituents, some of them only by a mere stereoisomerism such as GTX-2 and GTX-3. [2] [4] Gonyautoxins are detectable by means of High Performance Liquid Chromatography (HPLC), which has been tested on mice., [5] In 2009 a monoclonal antibody is developed to detect gonyautoxin 2 or 3 in aquatic products. The detection limit is measured to be lower than 0.74 micrograms per milliliter. [6]

Synthesis

While the gonyautoxins are naturally available, a synthesis procedure of some of them is known as well. Gonyautoxin 2 can for example be synthesized from L-serine methyl ester, via gonyautoxin 3. In this process firstly the L-serine methyl ester is treated with aldehyde, so that it can react to close the ring structure. The formed allyl is deprotected by the addition of [[SO3CH2CCl3]]. [7] Subsequently, a RH-catalyzed amination reaction with guanidine is followed, forming the tricyclic frame of GTX-3. The relatively unstable intermediates of several reactions in this process are modified by using three protecting groups. Removing these groups gives 11β-hydrosaxitoxin as a product, which will then be sulfated on the C 11-alcohol. GTX-2 is formed by incubating the product in an aqueous solution at pH 8, in order to make the epimerization at C11 still occur. [7]

Poisoning and illness

Toxicology

Like every saxitoxin, the gonyautoxins are neurotoxins and cause a disease known as paralytic shellfish poisoning (PSP). [3] For humans a dose of 1–4 mg of these toxins is already lethal. Shellfish can contain more than 10 micrograms of gonyautoxin per 100 gram weight, inducing that the consumption of a few mussels can already be fatal for human. Each year approximately 2000 cases of PSP are reported, of which about 15% end deadly. [8]

Mechanism of action

As neurotoxins, the gonyautoxins influence the nervous system. They can bind with high affinity at the site 1 of the α-subunit of the voltage dependent sodium channels in the postsynaptic membrane. These channels are responsible for initiating the action potentials, after the synapse. The binding of PSP toxins prevents the generation and propagation of these potentials and hence blocks the synaptic function. [9]

Symptoms

The symptoms are the typical symptoms of a shellfish toxication. It starts with prickling in the face, which will later spread out over the body. This will be followed by numbness and headaches. In extreme cases, the possibility of vertigos exists as well. Over time the pulse increases and muscle pain occurs. Furthermore, blindness and vision disorders are also possible symptoms. [1] Death is most likely to occur within the first twelve hours, caused by paralysis of the respiratory tract. Most patients who manage to keep up for this time, will survive the poisoning. [1]

Detoxification

Biotransformation in the human body occurs as a first phase detoxification by oxidizing the gonyautoxin molecule. The formed products are other oxidized forms of gonyautoxins. In the second phase detoxification step a glucuronidation takes place which produces glucuronic-GTX, which has an increased hydrophilicity in comparison to the GTX and can hence be excreted more easily. [9]

Treatment

Since no antitoxin has been found yet, the treatment is in first line symptomatic for a paralytic shellfish poisoning. Aside a possible artificial respiration, the treatment with charcoal is an option as well because shellfish toxins are likely to be absorbed by this substance. [1] Potentially the strongly discussed treatment with neostigmine, ephedrine, or DL-amphetamine can be helpful as well. [1]

Other uses

Gonyautoxins can be used as treatment against acute or chronic anal fissures. The toxins help the muscle to relax and hence kill the pain. In a study, the bleedings of the poisoned patients stopped within 48 hours. This is thanks to a temporary paralysis at the injection-area, which appears to last for over one week. [10]

See also

Related Research Articles

<span class="mw-page-title-main">Toxin</span> Naturally occurring organic poison

A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919) and is derived from the word "toxic".

<span class="mw-page-title-main">Algal bloom</span> Spread of planktonic algae in water

An algal bloom or algae bloom is a rapid increase or accumulation in the population of algae in freshwater or marine water systems. It is often recognized by the discoloration in the water from the algae's pigments. The term algae encompasses many types of aquatic photosynthetic organisms, both macroscopic multicellular organisms like seaweed and microscopic unicellular organisms like cyanobacteria. Algal bloom commonly refers to the rapid growth of microscopic unicellular algae, not macroscopic algae. An example of a macroscopic algal bloom is a kelp forest.

<span class="mw-page-title-main">Domoic acid</span> Chemical compound

Domoic acid (DA) is a kainic acid-type neurotoxin that causes amnesic shellfish poisoning (ASP). It is produced by algae and accumulates in shellfish, sardines, and anchovies. When sea lions, otters, cetaceans, humans, and other predators eat contaminated animals, poisoning may result. Exposure to this compound affects the brain, causing seizures, and possibly death.

<span class="mw-page-title-main">Cyanotoxin</span> Toxin produced by cyanobacteria

Cyanotoxins are toxins produced by cyanobacteria. Cyanobacteria are found almost everywhere, but particularly in lakes and in the ocean where, under high concentration of phosphorus conditions, they reproduce exponentially to form blooms. Blooming cyanobacteria can produce cyanotoxins in such concentrations that they can poison and even kill animals and humans. Cyanotoxins can also accumulate in other animals such as fish and shellfish, and cause poisonings such as shellfish poisoning.

<span class="mw-page-title-main">Saxitoxin</span> Paralytic shellfish toxin

Saxitoxin (STX) is a potent neurotoxin and the best-known paralytic shellfish toxin (PST). 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).

<span class="mw-page-title-main">Paralytic shellfish poisoning</span> Syndrome of shellfish poisoning

Paralytic shellfish poisoning (PSP) is one of the four recognized syndromes of shellfish poisoning, which share some common features and are primarily associated with bivalve mollusks. These shellfish are filter feeders and accumulate neurotoxins, chiefly saxitoxin, produced by microscopic algae, such as dinoflagellates, diatoms, and cyanobacteria. Dinoflagellates of the genus Alexandrium are the most numerous and widespread saxitoxin producers and are responsible for PSP blooms in subarctic, temperate, and tropical locations. The majority of toxic blooms have been caused by the morphospecies Alexandrium catenella, Alexandrium tamarense, Gonyaulax catenella and Alexandrium fundyense, which together comprise the A. tamarense species complex. In Asia, PSP is mostly associated with the occurrence of the species Pyrodinium bahamense.

<span class="mw-page-title-main">Brevetoxin</span> Class of chemical compounds produced naturally

Brevetoxin (PbTx), or brevetoxins, are a suite of cyclic polyether compounds produced naturally by a species of dinoflagellate known as Karenia brevis. Brevetoxins are neurotoxins that bind to voltage-gated sodium channels in nerve cells, leading to disruption of normal neurological processes and causing the illness clinically described as neurotoxic shellfish poisoning (NSP).

<i>Anabaena circinalis</i> Species of bacterium

Anabaena circinalis is a species of Gram-negative, photosynthetic cyanobacteria common to freshwater environments throughout the world. Much of the scientific interest in A. circinalis owes to its production of several potentially harmful cyanotoxins, ranging in potency from irritating to lethal. Under favorable conditions for growth, A. circinalis forms large algae-like blooms, potentially harming the flora and fauna of an area.

<span class="mw-page-title-main">Neurotoxic shellfish poisoning</span> Syndrome of shellfish poisoning

Neurotoxic shellfish poisoning (NSP) is caused by the consumption of brevetoxins, which are marine toxins produced by the dinoflagellate Karenia brevis. These toxins can produce a series of gastrointestinal and neurological effects. Outbreaks of NSP commonly take place following harmful algal bloom (HAB) events, commonly referred to as "Florida red tide". Algal blooms are a naturally-occurring phenomenon, however their frequency has been increasing in recent decades at least in-part due to human activities, climate changes, and the eutrophication of marine waters. HABs have been occurring for all of documented history, evidenced by the Native Americans' understanding of the dangers of shellfish consumption during periods of marine bioluminescence. Blooms have been noted to occur as far north as North Carolina and are commonly seen alongside the widespread death of fish and sea birds. In addition to the effects on human health, the economic impact of HAB-associated shellfish toxin outbreaks can have significant economic implications as well due to not only the associated healthcare costs, but the adverse impact on the commercial shellfish industry.

<i>Leukoma staminea</i> Species of bivalve

Leukoma staminea, commonly known as the Pacific littleneck clam, the littleneck clam, the rock cockle, the hardshell clam, the Tomales Bay cockle, the rock clam or the ribbed carpet shell, is a species of bivalve mollusc in the family Veneridae. This species of mollusc was exploited by early humans in North America; for example, the Chumash peoples of Central California harvested these clams in Morro Bay approximately 1,000 years ago, and the distinctive shells form middens near their settlements.

<span class="mw-page-title-main">Harmful algal bloom</span> Population explosion of organisms that can kill marine life

A harmful algal bloom (HAB), or excessive algae growth, is an algal bloom that causes negative impacts to other organisms by production of natural algae-produced toxins, mechanical damage to other organisms, or by other means. HABs are sometimes defined as only those algal blooms that produce toxins, and sometimes as any algal bloom that can result in severely lower oxygen levels in natural waters, killing organisms in marine or fresh waters. Blooms can last from a few days to many months. After the bloom dies, the microbes that decompose the dead algae use up more of the oxygen, generating a "dead zone" which can cause fish die-offs. When these zones cover a large area for an extended period of time, neither fish nor plants are able to survive. Harmful algal blooms in marine environments are often called "red tides".

Alexandrium tamarense is a species of dinoflagellates known to produce saxitoxin, a neurotoxin which causes the human illness clinically known as paralytic shellfish poisoning (PSP). Multiple species of phytoplankton are known to produce saxitoxin, including at least 10 other species from the genus Alexandrium.

<i>Zosimus aeneus</i> Species of crab

Zosimus aeneus, also known as the devil crab, toxic reef crab, and devil reef crab is a species of crab that lives on coral reefs in the Indo-Pacific from East Africa to Hawaii. It grows to a size of 60 mm × 90 mm and has distinctive patterns of brownish blotches on a paler background. It is potentially lethal due to the presence of the neurotoxins tetrodotoxin and saxitoxin in its flesh and shell.

<span class="mw-page-title-main">Neosaxitoxin</span> Chemical compound

Neosaxitoxin (NSTX) is included, as other saxitoxin-analogs, in a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs). The parent compound of PSTs, saxitoxin (STX), is a tricyclic perhydropurine alkaloid, which can be substituted at various positions, leading to more than 30 naturally occurring STX analogues. All of them are related imidazoline guanidinium derivatives.

<i>Alexandrium</i> (dinoflagellate) Genus of single-celled organisms

Alexandrium is a genus of dinoflagellates. It contains some of the dinoflagellate species most harmful to humans, because it produces toxic harmful algal blooms (HAB) that cause paralytic shellfish poisoning (PSP) in humans. There are about 30 species of Alexandrium that form a clade, defined primarily on morphological characters in their thecal plates.

<i>Saxidomus gigantea</i> Species of bivalve

Saxidomus gigantea is a large, edible saltwater clam, a marine bivalve mollusk in the family Veneridae, the venus clams. It can be found along the western coast of North America, ranging from the Aleutian Islands to San Francisco Bay. Common names for this clam include butter clam, Washington clam, smooth Washington clam and money shell.

Alexandrium catenella is a species of dinoflagellates. It is among the group of Alexandrium species that produce toxins that cause paralytic shellfish poisoning, and is a cause of red tide. Alexandrium catenella is observed in cold, coastal waters, generally at temperate latitudes. These organisms have been found in the west coast of North America, Japan, Australia, and parts of South Africa.

Dinotoxins are a group of toxins which are produced by flagellate, aquatic, unicellular protists called dinoflagellates. Dinotoxin was coined by Hardy and Wallace in 2012 as a general term for the variety of toxins produced by dinoflagellates. Dinoflagellates are an enormous group of marine life, with much diversity. With great diversity comes many different toxins, however, there are a few toxins that multiple species have in common.

Canadian Reference Materials (CRM) are certified reference materials of high-quality and reliability produced by the National Metrology Institute of Canada – the National Research Council Canada. The NRC Certified Reference Materials program is operated by the Measurement Science and Standards portfolio and provides CRMs for environmental, biotoxin, food, nutritional supplement, and stable isotope analysis. The program was established in 1976 to produce CRMs for inorganic and organic marine environmental analysis and remains internationally recognized producer of CRMs.

<span class="mw-page-title-main">Decarbamoylsaxitoxin</span> Chemical compound

Decarbamoylsaxitoxin, abbreviated as dcSTX, is a neurotoxin which is naturally produced in dinoflagellate. DcSTX is one of the many analogues of saxitoxin (STX).

References

  1. 1 2 3 4 5 Habermehl, G. (2013). Gift-Tiere und ihre Waffen: Eine Einführung für Biologen, Chemiker und Mediziner Ein Leitfaden für Touristen.
  2. 1 2 3 The Human Metabolome Database
  3. 1 2 Christophersen, C. (24 May 1986). "Marine Alkaloids". The Alkaloids: Chemistry and Pharmacology. 24.
  4. Toronto Research Chemicals website
  5. Ledochowski, M. (2010). Klinische Ernährungsmedizin.
  6. Tang, Y.; Wang, H.; Xiang, J.; Chen, Y.; He, W.; Deng, N.; Yang, H. (2009). "A sensitive immunosorbent bio-barcode assay combining PCR with icELISA for detection of gonyautoxin 2/3". Analytica Chimica Acta. 657 (2): 210–214. doi:10.1016/j.aca.2009.10.045.
  7. 1 2 Mulcahy, V. M.; Du Bois, J. (2008). A Stereoselective Synthesis of (+)-Gonyautoxin 3.
  8. Van Dolah, F. M. (2000). "Marine algal toxins: origins, health effects, and their increased occurrence". Environmental Health Perspectives. 108 (Suppl 1): 133–141. doi:10.1289/ehp.00108s1133. PMC   1637787 . PMID   10698729.
  9. 1 2 Andrinolo, D.; Michea, L. F.; Lagos, N. (1999). "Toxic effects, pharmacokinetics and clearance of saxitoxin, a component of paralytic shellfish poison (PSP), in cats". Toxicon. 37 (3): 447–464. doi:10.1016/s0041-0101(98)00173-1. hdl: 10533/197637 . PMID   10080350.
  10. Garrido, R.; Lagos, N.; Lattes, K.; Abedrapo, M.; Bocic, G.; Cuneo, A.; Chiong, H.; Jensen, C.; Azolas, R.; Henriquez, A.; Garcia, C. (2005). "Gonyautoxin: new treatment for healing acute and chronic anal fissures". Diseases of the Colon and Rectum. 48 (2): 335–340. doi:10.1007/s10350-004-0893-4.