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Amatoxins

The structure of amanine , one of the representatives of the amatoxin group

Amatoxins , also amanitins , amanitotoxins - a group of organic compounds , are cyclic peptides (octapeptides), consisting of eight amino acid residues . All toxins of amanite contain Ξ³-hydroxylated amino acids, which is a condition for their toxicity [1] . Extremely toxic, the strongest hepatotoxins infect liver cells ( hepatocytes ), causing their necrosis , and thereby pose a great threat to human health and life during intoxication. Found in the fruiting bodies of fungi of the genus Amanita , Galerina and Lepiot .

Content

Sources of Amatoxins

Sources of amatoxins are some types of fungi of the genus Amanita ( pale grebe , grebe , toadstool , spring grebe , etc.), Galerin ( galerine bordered , etc.) and Lepiot or Cheshuynitsa ( brown-red lepiot, chestnut lepiota, pinkish lepiota , etc.).

The most common and deadly mushrooms containing amatoxins:

  •  

    Lepiota is brownish red, one of the deadliest mushrooms of its kind.

  •  

    Galerine-bordered, deadly poisonous mushroom.

  •  

    White grebe or white fly agaric, one of the deadly species of fungi of the genus Amanita.

  •  

    Chestnut Lepiota, another deadly mushroom containing large amounts of amatoxins.

  •  

    Pale grebe ( Amanita phalloides ), the most common deadly poisonous mushroom of the genus Amanita. Amatoxins were first discovered in this fungus, from where they got their name.

Building

 
The structure of amatoxins. The skeleton of the structure, which is constant for all species, is indicated in black. Variable (variable) groups R 1 - R 5 , indicated in red, determine specific types of amatoxins

In total, ten types of amatoxins are known, presented in the form of a table [2] :

TitleR 1R 2R 3R 4R 5
Ξ±-amanitineOHOHNH 2OHOH
Ξ²-amanitineOHOHOHOHOH
Ξ³-amanitineHOHNH 2OHOH
Ξ΅-amanitineHOHOHOHOH
AmanullinHHNH 2OHOH
Amanullic acidHHOHOHOH
AmaninamideOHOHNH 2HOH
AmaninOHOHOHHOH
ProamanullinHHNH 2OHH

Toxicology

 

All amatoxins - SDYAV , with a pronounced cytotoxic effect. They cause destruction (destruction) of gastric cells and especially intestinal enterocytes . The most sensitive to the effects of amatoxins are liver and kidney cells. However, exposure is slow. The minimum lethal dose ranges from 0.1 mg to 7 mg / kg of the human body.

Amatoxins are easily absorbed by the digestive tract and are distributed throughout the human body. More than 50% is deposited by the liver , which is the main target of toxins. A smaller portion is deposited by kidney cells (average <3%).

Acute Poisoning

The first signs of acute poisoning with amatoxins are observed after 6-30 hours (long latent period), after the use of poisonous mushrooms , since their effect is slow and depends on the quantity. Symptoms occur suddenly: severe vomiting (persistent), abdominal pain, diarrhea , tenesmus . Blood is observed in the stool (since the destruction of intestinal enterocytes occurs). Weakness, disturbances in the water-electrolyte balance are growing. On the 2nd - 3rd day, signs of toxic hepatopathy develop ( hepatomegaly - enlargement of the liver), jaundice , hemorrhagic diathesis , nephropathy , liver and kidney failure (hepatargy, anuria , coma ). Extremely severe poisoning occurs in children, it is especially dangerous if a large amount of toxins (more than 50 mg) has been ingested.

According to the severity of intoxication can be divided into:

  • lungs (20% of cases) - moderately expressed: manifestations of gastroenteritis , mild hepatopathy;
  • moderate severity (30% of cases) - severe gastroenteritis, moderate hepatopathy, mild or moderate nephropathy ;
  • severe (50% of cases, the most likely) - pronounced gastroenteritis, severe hepatopathy, nephropathy with the development of acute liver failure.

Lightning-fast forms of the course are possible, especially in children, with the development of acute liver atrophy and a quick fatal outcome. The main cause of death is acute liver failure, less commonly acute liver and kidney failure (ARF). With intoxications with amatoxins, irreversible changes in the structure of the liver tissue occur, expressed by total necrosis .

Molecular Mechanism of Impact

Amatoxins are powerful and selective inhibitors of RNA polymerase II , a vital enzyme in the synthesis of messenger RNA (mRNA), miRNAs, and small nuclear RNAs (snRNAs). Without mRNA, which is a template for protein synthesis, cell metabolism stops and lysis occurs [3] . Pale toadstead RNA polymerase ( Amanita phalloides ) is insensitive to the effects of amatoxins; thus, the autointoxication of the fungus does not occur [4] .

Precautions

 
Pale grebe can be very similar to some types of russula

Most often, amatoxin intoxications occur when eating poisonous mushrooms of the genus Amanita, the most common of which is pale grebe.

Pale grebe is similar to some types of edible mushrooms - russula , champignons , greenfinch and others, as a result of this many inexperienced mushroom pickers may carry out erroneous collection. In order to avoid intoxication with a pale grebe - in no case is it recommended to pick mushrooms without an experienced mushroom picker !

Notes

  1. ↑ Barton D., Ollis W. D. General Organic Chemistry. - M .: Chemistry, 1986. - S. 317. - 704 p.
  2. ↑ K. Baumann K. Muenter H. Faulstich. Identification of structural features involved in binding of Ξ±-amanitin to a monoclonal antibody (Eng.) // Biochemistry: journal. - 1993. - Vol. 32 , no. 15 . - P. 4043-4050 . - DOI : 10.1021 / bi00066a027 . - PMID 8471612 .
  3. ↑ Karlson-Stiber C., Persson H. Cytotoxic fungi - an overview (English) // Toxicon : journal. - 2003. - Vol. 42 , no. 4 . - P. 339β€”349 . - DOI : 10.1016 / S0041-0101 (03) 00238-1 . - PMID 14505933 .
  4. ↑ Horgen, Paul A .; Vaisius, Allan C .; Ammirati, Joseph F. The insensitivity of mushroom nuclear RNA polymerase activity to inhibition by amatoxins (English) // Archives of Microbiology : journal. - 1978. - Vol. 118 , no. 3 . - P. 317-319 . - DOI : 10.1007 / BF00429124 . - PMID 567964 .

See also

  • Phallotoxins
  • Mushroom poisoning
  • Amanita
Source - https://ru.wikipedia.org/w/index.php?title=Amatoxins&oldid=101062053


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