Α-Amanitin

Alpha-Amanitin–RNA polymerase II complex 1K83

Α-Amanitin is a highly potent toxin found in several species of the mushroom genus Amanita, most notably the Death Cap (Amanita phalloides) and the Destroying Angels (Amanita virosa and Amanita bisporigera). It is one of the principal toxins responsible for the lethality of these mushrooms. Α-Amanitin works by inhibiting RNA polymerase II, a critical enzyme in the synthesis of mRNA, miRNA, and snRNA. This inhibition disrupts the essential process of transcription in eukaryotic cells, leading to cell death.

Chemical Structure and Mechanism

Α-Amanitin is a cyclic peptide of eight amino acids. Its ability to inhibit RNA polymerase II is due to its tight binding to the enzyme, preventing the elongation of the RNA chain. Unlike many other mushroom toxins, which affect the liver and kidneys indirectly, α-amanitin directly affects the nucleus of cells, causing severe damage to the liver and kidneys due to their high metabolic rates.

Symptoms of Poisoning

The symptoms of poisoning by α-amanitin containing mushrooms are severe and can be fatal. They are typically delayed, not appearing until 6 to 24 hours after ingestion. Initial symptoms include severe abdominal pain, vomiting, and diarrhea, which can lead to dehydration and electrolyte imbalance. After a brief period of apparent recovery, liver and kidney failure may occur, leading to death if not treated promptly.

Treatment

There is no specific antidote for α-amanitin poisoning. Treatment is primarily supportive and aims to reduce the toxin's absorption, support liver function, and prevent kidney failure. This may include the use of activated charcoal, aggressive hydration, and the administration of penicillin G and silymarin, the latter of which is derived from the milk thistle plant and has shown some efficacy in protecting liver cells from damage.

Prevention

Prevention of α-amanitin poisoning is primarily through education and avoidance of consuming wild mushrooms unless absolutely certain of their identity. Mushroom foragers are advised to seek expert guidance and make use of comprehensive field guides when identifying mushrooms.

Legal Status and Research

Research into α-amanitin is ongoing, with studies focusing on its mechanism of action and potential uses in cancer therapy, exploiting its ability to inhibit RNA polymerase II selectively in tumor cells. However, its legal status varies by country, with regulations typically governing the collection and sale of wild mushrooms.