Amatoxin

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Amatoxins are a subgroup of at least eight toxic compounds found in several genera of poisonous mushrooms, most notably Amanita phalloides and several other members of the genus Amanita, as well as some Conocybe, Galerina and Lepiota mushroom species.

Structure

The compounds have a similar structure, that of eight amino-acid residues arranged in a conserved macrobicyclic motif (an overall pentacyclic structure when counting the rings inherent in the proline and tryptophan-derived residues); they were isolated in 1941 by Heinrich O. Wieland and Rudolf Hallermayer of the University of Munich.[1] All amatoxins are oligopeptides that are synthesized as 35-amino-acids-long proproteins, from which the final eight amino acids are cleaved by a prolyl oligopeptidase.[2]

The backbone structure (black) is the same in all the amatoxins and five variable groups (red) determine the specific compound.

There are currently ten known amatoxins:[3]

Name R1 R2 R3 R4 R5
α-Amanitin OH OH NH2 OH OH
β-Amanitin OH OH OH OH OH
γ-Amanitin H OH NH2 OH OH
ε-Amanitin H OH OH OH OH
Amanullin H H NH2 OH OH
Amanullinic acid H H OH OH OH
Amaninamide OH OH NH2 H OH
Amanin OH OH OH H OH
Proamanullin H H NH2 OH H

δ-Amanitin has been reported, but its chemical structure has not been determined.

Mechanism

Their major toxic mechanism is the inhibition of RNA polymerase II, a vital enzyme in the synthesis of messenger RNA (mRNA), microRNA, and small nuclear RNA (snRNA). Without mRNA, essential protein synthesis, and hence cell metabolism, grind to a halt and the cell dies.[4]

Clinical symptoms

The liver is the principal organ affected, as it is the organ which is first encountered after absorption in the gastrointestinal tract, though other organs, especially the kidneys, are susceptible.[5] The RNA polymerase of Amanita phalloides is insensitive to the effects of amatoxins; thus, the mushroom does not poison itself.[6]

The estimated minimum lethal dose is 0.1 mg/kg or 7 mg of toxin in adults. Their swift intestinal absorption coupled with their thermostability leads to rapid development of toxic effects in a relatively short period of time. The most severe effects are toxic hepatitis with centrolobular necrosis and hepatic steatosis, as well as acute tubulointerstitial nephropathy, which altogether induce a severe hepatorenal syndrome.

Treatment

Treatment involves high dose penicillin as well as supportive care in cases of hepatic and renal injury. Silibinin, a product found in milk thistle, is a potential antidote to amatoxin poisoning, although more data needs to be collected. Cautious attention is given to maintaining hemodynamic stability, although if hepatorenal syndrome has developed the prognosis is guarded at best.[7]

Detection

Presence of amatoxins in mushroom samples may be detected by the Meixner Test (also known as the Wieland Test). The amatoxins may be quantitated in plasma or urine using chromatographic techniques to confirm a diagnosis of poisoning in hospitalized patients and in postmortem tissues to aid in a medicolegal investigation of a suspected fatal overdosage.[8]

See also

References

  1. ^ Litten, W. (1975). "The most poisonous mushrooms". Scientific American. 232 (3): 90–101. doi:10.1038/scientificamerican0375-90. PMID 1114308. {{cite journal}}: Unknown parameter |month= ignored (help)
  2. ^ H. E. Hallen, H. Luo, J. S. Scott-Craig, and J. D. Walton (2007). "Gene family encoding the major toxins of lethal Amanita mushrooms". Proceedings of the National Academy of Sciences USA. 104 (48): 19097–19101. doi:10.1073/pnas.0707340104. PMC 2141914. PMID 18025465.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ^ K. Baumann, K. Muenter, and H. Faulstich (1993). "Identification of structural features involved in binding of α-amanitin to a monoclonal antibody". Biochemistry. 32 (15): 4043–4050. doi:10.1021/bi00066a027. PMID 8471612.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Karlson-Stiber C, Persson H (2003). "Cytotoxic fungi - an overview". Toxicon. 42 (4): 339–49. doi:10.1016/S0041-0101(03)00238-1. PMID 14505933.
  5. ^ Benjamin.p217
  6. ^ Horgen, Paul A. (1978). "The insensitivity of mushroom nuclear RNA polymerase activity to inhibition by amatoxins". Archives of Microbiology. 118 (3): 317–9. doi:10.1007/BF00429124. PMID 567964. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  7. ^ Piqueras J. (1989). "Hepatotoxic mushroom poisoning: diagnosis and management". Mycopathologia. 105 (2): 99–110. PMID 2664527.
  8. ^ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 52–54.
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