Amatoxin

Amatoxin is the collective name of 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.

[3] The schematic amino acid sequence of amatoxins is Ile-Trp-Gly-Ile-Gly-Cys-Asn-Pro with cross-linking between Trp and Cys via the sulfoxide (S=O) moiety and hydroxylation in variants of the molecule; enzymes for these processings steps remain unknown.

[10] 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.

[16] More specifically, exposure to amatoxins may cause irritation of the respiratory tract, headache, dizziness, nausea, shortness of breath, coughing, insomnia, diarrhea, gastrointestinal disturbances, back pain, urinary frequency, liver and kidney damage, or death if ingested or inhaled.

[17] Persons with pre-existing skin, eye, or central nervous systems disorders, impaired liver, kidney, or pulmonary function may be more susceptible to the effects of this substance.

Their swift intestinal absorption coupled with their thermostability leads to rapid development of toxic effects in a relatively short period of time.

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.

[23][24] In 2010 a study on Amanita bisporigera, the destroying angel, determined that the concentrations of toxins in the spores were also lower than the levels found in the cap or stipe.

[26] Additionally, amatoxins decompose very slowly when stored in open, aqueous solutions or following prolonged exposure to sun or neon light.

[26] 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.

[27] Previous studies have demonstrated that younger mushrooms can contain a higher concentration of toxins than is found in mature specimens.

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.

The backbone structure (black) is the same in all the amatoxins and five variable groups (red) determine the specific compound.
Ribbon diagram of RNA polymerase II molecule showing central binding site of alpha-amanitin molecule
α-Amanitin (red) bound to RNA polymerase II from Saccharomyces cerevisiae (brewer's yeast). From PDB : 1K83 ​. [ 11 ]