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Amatoxins are a subgroup of at least nine related cyclic peptide toxins found in three genera of deadly poisonous mushrooms ( Amanita, Galerina and Lepiota) and one species of the genus Pholiotina. Amatoxins are very potent, as little as half a mushroom cap can cause severe liver injury if swallowed.
There are currently ten named amatoxins:
| alpha-Amanitin | OH | OH | NH2 | OH | OH |
| beta-Amanitin | OH | OH | OH | OH | OH |
| gamma-Amanitin | OH | H | NH2 | OH | OH |
| epsilon-Amanitin | OH | H | 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.
Amatoxins are able to travel through the bloodstream to reach the organs in the body. While these compounds can damage many organs, damage to the liver and heart result in fatalities. At the molecular level, amatoxins cause damage to cells of these organs by causing perforations in the plasma membranes resulting in misplaced organelles that are normally in the cytoplasm to be found in the extracellular matrix. beta-Amanitin is also an inhibitor of eukaryotic RNA polymerase II and RNA polymerase III, and as a result, mammalian protein synthesis. It has not been found to inhibit RNA polymerase I or bacterial RNA polymerase. Because it inactivates the RNA polymerases, the liver is unable to repair damage and the cells of the liver die off quickly.
Alpha-amanitin (α-Amanitin) primarily affects the bridge helix of the RNA pol II complex, a highly conserved domain 35 amino acids long. At the N-terminus and the C-terminus of this region there are hinge structures that undergo significant conformational changes throughout the nucleotide addition cycle, and are essential for its progression. One of the many roles of the bridge helix is facilitating the translocation of DNA. Alpha-amanitin binds to the bridge helix of the RNA Pol II complex and it also binds to part of the complex that is adjacent to the bridge helix, while it is in one specific conformation. This binding locks the bridge helix into place, dramatically slowing its movement in translocating the DNA. The rate of pol II translocation of DNA is reduced from several thousand to a few nucleotides per minute.
The estimated minimum lethal dose is 0.1 mg/kg or 7 to 10 milligrams 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 severe liver failure and kidney failure.
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.
In 2020, a monoclonal antibody-based lateral flow immunoassay has been developed that can quickly and selectively detect amatoxins. This test sensitively detects Alpha-Amanitin and Gamma-Amanitin (clearly detects 10 ng/mL), and exhibits slightly less detection for beta-amanitin (0.5% cross-reactivity; 2000 ng/mL). Although this test cross-reacts with at 0.005% (200,000 ng/mL), the phallotoxins would not interfere in urine sampling and there are very rare instances where a mushroom produces phallotoxins without producing amatoxins.
Amatoxins are extremely toxic to humans with Amanita phalloides and its variants making up many of the cases of fatal toxicity after consumption.These toxins have high heat stability and this property combined with their solubility in water make them exceptionally toxic as they are not destroyed by cooking or drying. In addition, amatoxins are resistant to enzyme and acid degradation, and therefore when ingested they are not inactivated in the gastrointestinal tract. A fatal case was reported after consuming A. phalloides that had been frozen for 7–8 months, thus demonstrating that these compounds are also resistant to the freeze/thawing processes. Additionally, amatoxins decompose very slowly when stored in open, aqueous solutions or following prolonged exposure to sun or neon light.
In 2015, a case study was conducted on a patient who cooked and consumed just the caps from two Amanita phalloides mushrooms and was subsequently admitted to hospital a day later. The subject was a 61-year-old man with a body weight of 67 kg who was presenting with fatigue, abdominal pain, nausea, vomiting and diarrhea. Mushrooms were collected from the same region and shown to the patient in order to confirm that these were what he had eaten and two mushrooms of approximately the same size and level of maturity were selected for study. Previous studies have demonstrated that younger mushrooms can contain a higher concentration of toxins than is found in mature specimens. The combined weight of the caps of these two mushrooms was 43.4g fresh or 4.3g when dry and when tested were found to contain a total of 21.3 mg of amatoxin distributed as 11.9 mg alpha-amanitin, 8.4 mg beta-amanitin and 1 mg gamma-amanitin. Analysis of the patient's urine after 4 days of treatment in hospital showed a concentration of 2.7 ng/ml alpha-amanitin and 1.25 ng/ml beta-amanitin with no gamma-amanitin detected. The patient survived and was discharged after 9 days of treatment with follow up tests showing no signs of liver damage but based on this case it was estimated that an oral dose of 0.32 mg amatoxin per kg of body mass could be lethal with an approximate lethal dose of alpha-amanitin being 0.2 mg/kg when taken orally. It was estimated that consuming more than 50g of fresh Amanita phalloides, roughly 2 medium-sized mushrooms could be deadly. Clinical tests showed that the amount consumed by the patient remained below the hypothetical lethal dose, which the study notes probably varies depending on patient health, predisposition to liver damage and regional variation in toxin concentrations.
Anecdotes have been repeated in field guides that claim foragers have fallen ill from spores alone after collecting toxic Amanita species in the same basket, unwittingly leaving their spores to collect on the harvest before the toxic ones were discarded. This subject however has not been researched and studies make no claims one way or the other as to the possibility of poisoning from spores alone. Given that the concentration of toxins found in the spores is lower than that of the cap, it would require the consumption of a substantial mass of spores, in excess of the weight of the mushroom caps themselves, in order to reach a fatal dose.
| Lepiota brunneoincarnata |
| Lepiota brunneolilacea |
| Lepiota castanea |
| Lepiota clypeolaria |
| Lepiota clypeolarioides |
| Lepiota felina |
| Lepiota fulvella |
| Lepiota fuscovinacea |
| Lepiota griseovirens |
| Lepiota heimii |
| Lepiota helveoloides |
| Lepiota kuehneri |
| Lepiota langei |
| Lepiota lilacea |
| Lepiota locanensis |
| Lepiota ochraceofulva |
| Lepiota pseudohelveola |
| Lepiota pseudolilacea |
| Lepiota rufescens |
| Lepiota subincarnata |
| Lepiota xanthophylla |
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