Poisoning Amanitin

Common Name(s) Death Angel Poison Amanitin... 

RNA pol II is essential for proper function of cells in all tissues and organs, but potentially fatal liver and kidney failure is the main risk for victims of a-amanitin poisoning. 

Many small peptides exert their effects at very low concentrations. For example, a number of vertebrate hormones (Chapter 23) are small peptides. These include oxytocin (nine amino acid residues), which is secreted by the posterior pituitary and stimulates uterine contractions bradykinin (nine residues), which inhibits inflammation of tissues and thyrotropin-releasing factor (three residues), which is formed in the hypothalamus and stimulates the release of another hormone, thyrotropin, from the anterior pituitary gland. Some extremely toxic mushroom poisons, such as amanitin, are also small peptides, as are many antibiotics. 

Amanitin. Toxin from poisonous mushroom Aminita phalloides... 

The eukaryotic RNA polymerases are not inhibited by rifamycin, but RNA polymerases II and III are completely inhibited by the mushroom poison a-amanitin (see Box 28-B). Inhibitors of DNA gyrase (Chapter 27) also interfere with transcription as do chain terminators such as cordycepin (3 -deoxyadenosine) and related nucleosides. 

The most useful inhibitor of eukaryotic transcription has been a-amanitin, a major toxic substance in the poisonous mushroom Amanita phalloides. The toxin preferentially binds to and inhibits RNA polymerase II (see table 28.4). At high concentrations it also can inhibit RNA polymerase III but not RNA polymerase I or bacterial, mitochondrial, or chloroplast RNA polymerases. 

Another class of toxins produced by some mushrooms consists of polypeptides, particularly amanitin and phalloidin. These substances are stable to heating (cooking). They are systemic poisons that attack cells of various organs, including the heart and liver. In early 1988, an organ transplant was performed on a woman in the U.S. to replace her liver, which was badly damaged from the ingestion of wild mushrooms that she and a companion had mistakenly identified as edible varieties and consumed. 

The phallotoxins 106, e.g. phalloidin, and the amatoxins 107, e.g. a-amanitin, produced by Amanita phalloides or death cup, are among the best-known peptide poisons 233). 

Eukaryotic cells contain at least four different DNA-dependent RNA polymerases. Their localization, cellular transcripts, and susceptibility to the cyclic octapeptide a-amanitin (derived from poisonous mushrooms) are shown in Table 11.3. a-Amanitin blocks the elongation phase of RNA synthesis. Although the structures of these enzymes are much more complex than that of the prokaryotic RNA polymerase, the basic mechanism is very similar to that of the prokaryotic enzyme. 

Figure 28.16. RNA Polymerase Poison. Amanita phalloides, a poisonous mushroom that produces a-amanitin. [After G. Lincoff and D. H. Mitchel, Toxic and Hallucinogenic Mushroom Poisoning (Van Nostrand Reinhold, 1977), p. 30.]...

The mode of action of mushroom-produced mycotoxins varies considerably. Alpha amanitin, amatoxin produced by some species of Amanita, is a class A poison that acts by inhibiting a critical nuclear polymerase that enables the cell to make protein. Once the function of this RNA polymerase is curtailed, basic life processes cease. Attempts to kill alpha amanitin with antibodies have proven to be even more harmful to patients than the poison itself. Most forms of mushroom poisoning can be treated with rapid lavage (induced vomiting) or medically approved ingestion of charcoal to absorb the toxin before it is absorbed into the stomach. 

B. The poison in poisonous mushrooms is a-amanitin, an inhibitor of eukaryotic RNA polymerases. 

MILK THISTLE Silybi marianae fructus, which is the fruit of Silibum marianum (L.) Gaert, family Asteraceae. The active ingredient in the fruit is silymarin (a mixture of isomeric flavonolignans with silibinin (silybin) as the most active substance, effective as an antidote to poisoning with fly agaric (phalloi-din and a-amanitin). 

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