Mushroom Phalloidine

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. 

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... 

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. 

Liver failure and Mushrooms - "Death Amatoxin and phalloidin... 

The same mushrooms contain several fast-acting toxic heptapeptides, the phalloidins, whose structures are similar to those of the amanitins. However, they contain a reduced sulfur atom (—S—) in the cross-bridge. They are specifically toxic to the liver.c The same mushrooms also contain an antidote to the phalloidins, antamanide. This cyclic... 

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). 

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. 

Phalloidin and related toxins found in some mushrooms, including Amanita phalloides, act by binding tightly to actin filaments and preventing cytoskeletal disassembly (Treinen-Moslen, 2001). 

Cytochalasins, drugs that inhibit cellular processes that require actin polymerization and depolymerization (e.g., phagocytosis, cytokinesis, clot retraction, etc.), also act by severing and capping actin filaments. Actin filaments can be stabilized by phalloidin, derived from the poisonous mushroom Amanita phalloides. Assembly of actin filaments into bundles (as in microvilli) and three-dimensional networks is accomplished by two groups of cross-linking proteins (Table 21-6). 

Death cap mushroom. Responsible for > 90% of mushroom deaths in the UK. Contains the peptides, amanitine and phalloidine. Hepato-toxic a-amanitine is the major toxic component. Direct attack on hepatocyte nuclei. Vomiting 8-12 h post-ingestion cramping abdominal pain diarrhoea. 2-3 days latent period then jaundice, circulatory collapse, haemorrhage, death. Death rate 30% in best hands . 

One should be very careful with field identification when collecting any mushroom to be eaten. This is especially tme in the present case, to avoid confusing Amanita muscaria or A. pantherina with one of their potentially lethal cousins. The deadly toxins alpha-wssadivA and phalloidin (and related cyclic polypeptides) have... 

O. 5 mg kg causes fiill protection of mice from death by phalloidin phallotoxins) after injection about 1 h before or, at the latest, simultaneously with 5 mg kg of the toxin. Antamanide is a competitive inhibitor of the transport system for phallotoxins and amatoxins in the parenchyma cells of the liver [Ih. Wieland, Peptides of Poisonous Amanita Mushrooms, Springer Series in Molecular Biology, Springer Ver-lag, Berlin, New York, 1986 K. Munster etal., Biochem. Biophys. Acta 1986, 860,91]. 

Muscarine from the mushroom. Amanita muse aria, has become a valuable biochemical tool for measuring peripheral effects on cholinergic receptors (see Volume 23 of this series). Each year Phalloidin from the mushroom. Amanita phalloides, causes several deaths in Europe from mushroom poisoning and has been the subject of a book by Theodor Wieland. In this volume, the subjects of alkaloids and mushrooms are brought together in a paper written by a team of experts from Poland in Alkaloids from Mushrooms. ... 

Similarly a thioether was first prepared in the synthesis of the toxic mushroom peptide phalloidin and the homodetic ring was closed only subsequently... 

Cytochalasin B (fungal toxin) and phalloidin (mushroom toxin) disrupt the microfibrillar system, causing canalicular paralysis and dilatation. 

Necrosis is often initiated by damage to membranes, either the plasma membrane of the cell or the membranes of organelles, particularly mitochondria (Zimmerman, 1999). Cell membrane damage is often caused by membrane phospholipid peroxidation. Plasma membrane damage interferes wi ion regulation, calcium homeostasis, energy production, and decrease in the ability of that organelle to sequester calcium. Inhibition of protein synthesis is an alternative mechanism that may cause cell necrosis. Toxins that act in this way include phalloidin and related mushroom toxins, which inhibit the action of ribonucleic acid (RNA) polymerase, and therefore mRNA synthesis (Pineiro-Carrero and Pineiro, 2004). 

Phalloidin is one of the poisons of the mushroom Amanita phaUoides with great toxicity. Only 50 pg are lethal for a mouse. Seven different amino acids are involved in its structure including such unusual hydroxy amino acids as hydroxy-leucine and allothreonine (T. Wieland). There is a bridge between tryptophan and the SH group of cysteine which yields hydroxy tryptophan upon hydrolysis. The formula is not reproduced here. 

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