Amanita phalloides

Phalloidin and phallacidin are cyclic peptides from the mushroom Amanita phalloides that stabilize F-actin. Phalloidin binds to residues 114-118 of an actin protomere and blocks nucleotide exchange without interfering with nucleotide hydrolysis. It enhances the rate of nucleation as well as that of elongation. It slowly penetrates the cell membrane and is used for immunocytochemical localization of F-actin. 

Poisoning and sometimes death from eating (unidentified) mushrooms is well known. In particular, Amanita sp. are particularly dangerous, with much emphasis on the death cap fungus , Amanita phalloides.24 The best known toxins are the amatoxins and phallotoxins, which are complex, bicyclic peptides. An unusual feature relates to sulfur a tryptophan (or substituted tryptophan) unit is linked to a cysteine sulfur at the carbon atom next to the NH group of the pyrrole ring, forming the unit, -CH2-S-C(NH)=C, e.g. in... 

Several experimental approaches can be employed to determine the pool sizes of polymerised and non-polymerised actin. Firstly, the enzyme DNAse I is inhibited by monomeric (G) actin, but not by polymerised (F) actin. Secondly, polymerised actin can be directly visualised by use of fluorescent derivatives of phalloidin, a cyclic peptide isolated from the toadstool Amanita phalloides that selectively binds to polymerised actin with high affinity. 

Labeled phallotoxines (phalloidins) The bicyclic peptides isolated from Amanita phalloides mushroom bind selectively to F-actin in nanomolar concentrations. They have advantages over antibodies for actin labeling... 

H Fungi - Amanita phalloides and Agaricus phalloides Cyanobacteria -Lyngbya majuscula Phalloidin, phallicidin, and amanitin - toxic peptides Majusculamide D - cytotoxic peptide Microcolin A - peptide with immunosuppressive, antileukemic and protein kinase C inhibitory activity 242... 

Children are also especially vnlnerable for a reason tonched npon in Chapter 2. Consider the family of mushroom toxins known as amatox-ins. Almost all mushroom-related deaths in North America are caused by these toxins, which are metabolic products of Amanita phalloides. These toxins are slightly unusual because symptoms appear only after 12 hours following ingestion they include vomiting, diarrhea, and very intense abdominal pain. Ultimately the toxins cause liver injury that can be serious enough to cause death. 

As individual G actin molecules are always oriented in the same direction relative to one another, F actin consequently has polarity, it has two different ends, at which polymerization takes place at different rates, if the ends are not stabilized by special proteins (as in muscle cells), then at a critical concentration of G actin the (+) end of F actin will constantly grow, while the (-) end simultaneously decays. These partial processes can be blocked by fungal toxins experimentally. Phalloidin, a toxin contained in the Amanita phalloides mushroom, inhibits decay by binding to the (-) end. By contrast, cytochalasins, mold toxins with cytostatic effects, block polymerization by binding to the (+) end. 

Transcription is catalyzed by DNA-dependent RNA polymerases. These act in a similar way to DNA polymerases (see p. 240), except that they incorporate ribonucleotides instead of deoxyribonucleotides into the newly synthesized strand also, they do not require a primer. Eukaryotic cells contain at least three different types of RNA polymerase. RNA polymerase I synthesizes an RNA with a sedimentation coef cient (see p. 200) of 45 S, which serves as precursor for three ribosomal RNAs. The products of RNA polymerase II are hnRNAs, from which mRNAs later develop, as well as precursors for snRNAs. Finally, RNA polymerase III transcribes genes that code for tRNAs, 5S rRNA, and certain snRNAs. These precursors give rise to functional RNA molecules by a process called RNA maturation (see p. 246). Polymerases II and III are inhibited by a-amanitin, a toxin in the Amanita phalloides mushroom. 

DETAILS - The toxicity of certain amanita mush rooms has been well known for centuries. The main toxic species in the United States are Amanita phalloides (Deathcupor Destroying Angel), A. verna, and A. virosa. They contain a mixture of the toxins amanitin, phallpidm, and phalloin. Heat weakens or destroys the toxins, as evidenced by the fact that fresh pressed Amanitajuice is three times more toxic than the boiled juice. There is no antidote for these toxins -treatment is largely symptomatic. The liver is the main target ana is virtually destroyed upon short... 

Ingestion of as little as 3 g of the death cap mushroom Amanita phalloides may constitute a lethal dose for some people. 

Delayed-onset mushroom poisoning, usually caused by Amanita phalloides, A virosa, Galerina autumnalis, or G marginata, manifests its first symptoms 6-12 hours after ingestion. Although the initial symptoms usually include nausea and vomiting, the major toxicity involves hepatic and renal cellular injury by amatoxins that inhibit RNA polymerase. Atropine is of no value in this form of mushroom poisoning (see Chapter 58). 

The skin often appears flushed, hot, and dry in poisoning with atropine and other antimuscarinics. Excessive sweating occurs with organophosphates, nicotine, and sympathomimetic drugs. Cyanosis may be caused by hypoxemia or by methemoglobinemia. Icterus may suggest hepatic necrosis due to acetaminophen or Amanita phalloides mushroom poisoning. 

Although milk thistle has not been confirmed as an antidote following acute exposure to liver toxins in humans, parenteral silybin is nevertheless marketed and used in Europe as an antidote in Amanita phalloides mushroom poisoning. This use is based on favorable outcomes reported in case-control studies. 

Other species of amanita are among the deadliest fungi known. Polypeptide-like toxins in Amanita phalloides, or death cup, can prove fatal or at the very least can cause permanent liver and kidney damage. These mushrooms are common in the temperate climates of Europe and North America. They are responsible for the majority of what is called "slow" mushroom poisoning in the U.S. In fact, it was only a few years ago that the local newspaper reported a case of amanita poisoning within SLO county. Mushroom poisoning is known as mycetism. In addition the amanita also contain bufotenine which has CNS effects. See the ASIDE which discusses the peptide poisons. 

The mushroom Amanita phalloides has evolved a very effective defense mechanism against predators. It produces a-amanitin, which disrupts mRNA formation in animal cells by blocking Pol II and, at higher concentrations, Pol III. Neither Pol I nor bacterial RNA polymerase is sensitive to a-amanitin—nor is the RNA polymerase II of A. phalloides itself ... 

Phenanthroline like 1,10- and 1,7-phenanthrolines has anticancer properties.374 The toxic effects of phalloidine, an isolate of the fungus Amanita phalloides, are inhibited by 4,7-phenanthroline.536 4,7-Phenanthroline also inhibits proline incorporation into proteins.391,392 3-Methyl-4,7-phenanthroline has been suggested as a diagnostic agent for assisting in the detection of blood in body fluids.537... 

Pattern of serum alanine aminotransferase (ALT) and bilirubin in the plasma, following poisoning with the toxic mushroom Amanita phalloides. 

Several deadly species of the genus Amanita produce colorless toxic octapeptides, the amani-tins.a b Two residues of glycine, one of L-isoleucine, one of the unusual L-dihydroxyisoleucine, one of L-asparagine, and one of L-hydroxyproline are present in a-amanitin. In the center a modified tryptophan residue has been combined oxidatively with an SH group of a cysteine residue. If the dihy-droxyisoleucine residue of a-amanitin is replaced with unhydroxylated leucine, the resulting compound, known as amanullin, is nontoxic. The LD50 for mice is 0.3 mg kg 1 and 50 g of fresh Amanita phalloides may be sufficient to kill a person. Arnan-itins act slowly, and it is impossible to kill mice in less than 15 h, no matter how high the dose. 

The poisonous components of the most deadly mushroom Amanita phalloides (the Death Cap) are bicyclic heptapeptides which have an additional covalent bond that connects the ( -sulfur atom of an l-cysteine residue with the carbon atom in position 2 of the indole ring of the L-tryptophan. Phalloidin (or phalloidine) is the most abundant member of a whole family of related cyclic heptapeptides called phallotoxins (for a review, see Wieland1 1). These poisonous peptides, therefore, contain a cross-linking moiety consisting of L-tryptophan coupled to L-cysteine, designated tryptathionine (1), alternatively called 5-(trypto-phan-2-yl)cysteine or 2-(L-3-alanylsulfenyl)-L-tryptophan (Scheme 1). 

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. 

Jacqueson A, Thevenin M, Wamet JM, et al. 1977. Sex influence on the experimental fatty liver induced by white phosphorus and Amanita phalloides in the rat. Acta Pharmacol Toxicol 41 322-329. 

Mushrooms are spore-forming bodies of filamentous terrestrial fungi, some of which are considered to be food delicacies, whereas others, such as Amanita phalloides, Amanita virosa, and Gyromita esculenta, are very toxic, with reported worldwide deaths of the order of 100 per year.10 In extreme cases, one bite of one poisonous mushroom can be fatal. Accidental mushroom poisonings are often caused by the death s head mushroom, because it is easily mistaken for edible varieties. 

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