Chemical structures
Phalloidin
Prophalloin
Phalloin
Phallisin
Phallacidin
Phallacin
Phallisacin
The phallotoxins consist of at least seven compounds, all of which are bicyclic heptapeptides (seven amino acids), isolated from the death cap mushroom (Amanita phalloides). They differ from the closely related amatoxins by being one residue smaller, both in the final product and the precursor protein. [1]
Phalloidin had been isolated in 1937 by Feodor Lynen, Heinrich Wieland's student and son-in-law, and Ulrich Wieland of the University of Munich. [2] [3] The remaining six are prophalloin, phalloin, phallisin, phallacidin, phallacin and phallisacin. Though highly toxic to liver cells, phallotoxins have since been found to have little contribution to the death cap's toxicity because they are not absorbed through the gut. Reports of phalloidin in the edible (and sought after) Blusher (Amanita rubescens) [4] have not been confirmed by later researchers [5]
Amanita phalloides, commonly known as the death cap, is a deadly poisonous basidiomycete fungus, one of many in the genus Amanita. Originating in Europe, but later introduced to other parts of the world since the late twentieth century, A. phalloides forms ectomycorrhizas with various broadleaved trees. In some cases, the death cap has been introduced to new regions with the cultivation of non-native species of oak, chestnut, and pine. The large fruiting bodies (mushrooms) appear in summer and autumn; the caps are generally greenish in colour with a white stipe and gills. The cap colour is variable, including white forms, and is thus not a reliable identifier.
The name destroying angel applies to several similar, closely related species of deadly all-white mushrooms in the genus Amanita. They are Amanita virosa in Europe and A. bisporigera and A. ocreata in eastern and western North America, respectively. Another European species of Amanita referred to as the destroying angel, Amanita verna—also referred to as the "Fool's mushroom"—was first described in France in 1780.
The genus Amanita contains about 600 species of agarics, including some of the most toxic known mushrooms found worldwide, as well as some well-regarded edible species. The genus is responsible for approximately 95% of fatalities resulting from mushroom poisoning, with the death cap accounting for about 50% on its own. The most potent toxin present in these mushrooms is α-Amanitin.
α-Amanitin (alpha-Amanitin) is a cyclic peptide of eight amino acids. It is possibly the most deadly of all the amatoxins, toxins found in several species of the mushroom genus Amanita, one being the death cap as well as the destroying angel, a complex of similar species, principally A. virosa and A. bisporigera. It is also found in the mushrooms Galerina marginata, Lepiota subincarnata and Conocybe filaris. The oral LD50 of amanitin is 100 μg/kg for rats.
Phalloidin belongs to a class of toxins called phallotoxins, which are found in the death cap mushroom (Amanita phalloides). It is a rigid bicyclic heptapeptide that is lethal after a few days when injected into the bloodstream. The major symptom of phalloidin poisoning is acute hunger due to the destruction of liver cells. It functions by binding and stabilizing filamentous actin (F-actin) and effectively prevents the depolymerization of actin fibers. Due to its tight and selective binding to F-actin, derivatives of phalloidin containing fluorescent tags are used widely in microscopy to visualize F-actin in biomedical research.
Heinrich Otto Wieland was a German chemist. He won the 1927 Nobel Prize in Chemistry for his research into the bile acids.
Mushroom poisoning is poisoning resulting from the ingestion of mushrooms that contain toxic substances. Symptoms can vary from slight gastrointestinal discomfort to death in about 10 days. Mushroom toxins are secondary metabolites produced by the fungus.
Amanita virosa is a species of fungus in the class Agaricomycetes. In the UK, it has the recommended English name of destroying angel and is known internationally as the European destroying angel. Basidiocarps are agaricoid (mushroom-shaped) and pure white with a ring on the stem and a sack-like volva at the base. The species is deadly poisonous. It occurs in Europe and northern Asia. Amanita virosa was formerly reported from North America, but research has shown that similar-looking American species, including Amanita bisporigera and A. ocreata, are distinct.
Amatoxin is the collective name of a subgroup of at least nine related toxic compounds found in three genera of poisonous mushrooms and one species of the genus Pholiotina. Amatoxins are very potent, as little as half a mushroom cap can cause severe liver injury if swallowed.
Galerina marginata, known colloquially as funeral bell, deadly skullcap, autumn skullcap or deadly galerina, is a species of extremely poisonous mushroom-forming fungus in the family Hymenogastraceae of the order Agaricales. It contains the same deadly amatoxins found in the death cap. Ingestion in toxic amounts causes severe liver damage with vomiting, diarrhea, hypothermia, and eventual death if not treated rapidly. About ten poisonings have been attributed to the species now grouped as G. marginata over the last century.
Amanita ocreata, commonly known as the death angel, destroying angel, angel of death or more precisely western North American destroying angel, is a deadly poisonous basidiomycete fungus, one of many in the genus Amanita. The large fruiting bodies generally appear in spring; the cap may be white or ochre and often develops a brownish centre, while the stipe, ring, gill and volva are all white. A. ocreata resembles several edible species commonly consumed by humans, increasing the risk of accidental poisoning. Mature fruiting bodies can be confused with the edible A. velosa, A. lanei or Volvopluteus gloiocephalus, while immature specimens may be difficult to distinguish from edible Agaricus mushrooms or puffballs.
γ-Amanitin (gamma-Amanitin) is a cyclic peptide of eight amino acids. It is an amatoxin, a group of toxins isolated from and found in several members of the mushroom genus Amanita, one being the death cap as well as the destroying angel, a complex of similar species, principally A. virosa and A. bisporigera. The compound is highly toxic, inhibits RNA polymerase II, disrupts synthesis of mRNA, and can be fatal.
Phallolysin is a protein found the Amanita phalloides species of the Amanita genus of mushrooms, the species commonly known as the death cap mushroom. The protein is toxic and causes cytolysis in many cells found in animals and is noted for its hemolytic properties. It was one of the first toxins discovered in Amanita phalloides when the various toxins in the species where first being researched. The protein itself is observed to come in 3 variations, with observed differences in isoelectric point. Cytolysis can be best described as being the destruction of cells, likely due to exposure from an external source such as pathogens and toxins. Hemolysis then follows a similar destructive pathway, but instead focuses specifically on the destruction of red blood cells. Phallolysin is known to be thermolabile, meaning that it is destroyed at high temperatures, and acid labile, meaning that it is easily broken down in acidic environments.
Antamanide is a cyclic decapeptide isolated from a fungus, the death cap: Amanita phalloides. It is being studied as a potential anti-toxin against the effects of phalloidin and for its potential for treating edema. It contains 1 valine residue, 4 proline residues, 1 alanine residue, and 4 phenylalanine residues with a structure of c(Val-Pro-Pro-Ala-Phe-Phe-Pro-Pro-Phe-Phe). It was isolated by determining the source of the anti-phalloidin activity from a lipophillic extraction from the organism. It has been shown that antamanide can react to form alkali metal ion complexes. These include complexes with sodium and calcium ions. When these complexes are formed, the cyclopeptide structure undergoes a conformational change.
Amanullinic acid is a cyclic nonribosomal peptide. It is an amatoxin, all of which are found in several members of the mushroom genus Amanita. Amanullinic acid is relatively non-toxic( oral LD50 >20 mg/kg in mice).
Amanita bisporigera is a deadly poisonous species of fungus in the family Amanitaceae. It is commonly known as the eastern destroying angel amanita, the eastern North American destroying angel or just as the destroying angel, although the fungus shares this latter name with three other lethal white Amanita species, A. ocreata, A. verna and A. virosa. The mushroom has a smooth white cap that can reach up to 10 centimetres across and a stipe up to 14 cm tall with a white skirt-like ring near the top. The bulbous stipe base is covered with a membranous sac-like volva. The white gills are free from attachment to the stalk and crowded closely together. As the species name suggests, A. bisporigera typically bears two spores on the basidia, although this characteristic is not immutable. A. bisporigera closely resembles a few other white amanitas, including the equally deadly A. virosa and A. verna.
Amanita exitialis, also known as the Guangzhou destroying angel, is a mushroom of the large genus Amanita. It is distributed in eastern Asia, and probably also in India where it has been misidentified as A. verna. Deadly poisonous, it is a member of section Phalloideae and related to the death cap A. phalloides. The fruit bodies (mushrooms) are white, small to medium-sized with caps up to 7 cm (2.8 in) in diameter, a somewhat friable ring and a firm volva. Unlike most agaric mushrooms which typically have four-spored basidia, the basidia of A. exitialis are almost entirely two-spored. Eight people were fatally poisoned in China after consuming the mushroom in 2000, and another 20 have been fatally poisoned since that incident. Molecular analysis shows that the species has a close phylogenetic relationship with three other toxic white Amanitas: A. subjunquillea var. alba, A. virosa and A. bisporigera.
Cytoskeletal drugs are small molecules that interact with actin or tubulin. These drugs can act on the cytoskeletal components within a cell in three main ways. Some cytoskeletal drugs stabilize a component of the cytoskeleton, such as taxol, which stabilizes microtubules, or Phalloidin, which stabilizes actin filaments. Others, such as Cytochalasin D, bind to actin monomers and prevent them from polymerizing into filaments. Drugs such as demecolcine act by enhancing the depolymerisation of already formed microtubules. Some of these drugs have multiple effects on the cytoskeleton: for example, Latrunculin both prevents actin polymerization as well as enhancing its rate of depolymerization. Typically the microtubule targeting drugs can be found in the clinic where they are used therapeutically in the treatment of some forms of cancer. As a result of the lack of specificity for specific type of actin, the use of these drugs in animals results in unacceptable off-target effects. Despite this, the actin targeting compounds are still useful tools that can be used on a cellular level to help further our understanding of how this complex part of the cells' internal machinery operates. For example, Phalloidin that has been conjugated with a fluorescent probe can be used for visualizing the filamentous actin in fixed samples.
Amanita fuliginea, commonly known as the east Asian brown death cap, is a species of deadly poisonous mushroom in the family Amanitaceae. The fruit bodies have convex, dark gray to blackish caps measuring 3–6 cm (1.2–2.4 in) in diameter. The gills, largely free from attachment to the stipe, are white and have short gills (lamellulae) interspersed. The spores are roughly spherical, amyloid, and typically measure 8–11 by 7–9.5 μm. The species was described as new to science by Japanese mycologist Tsuguo Hongo in 1953. A. fuliginea is classified in Amanita section Phalloideae, which contains the infamous destroying angel.
Virotoxins are monocyclic peptides formed by at least five different compounds: alaviroidin, viroisin, deoxoviroisin, viroidin, and deoxoviroidin. The structure and biological activity of virotoxins are similar to that of phallotoxins, thus suggesting that virotoxins are biosynthetically derived from phallotoxins or share common precursor pathways. As with phallotoxins, virotoxins are not considered to have significant toxic effects after oral exposure. At the molecular level, like phallotoxins, they interact with actin, stabilizing the bonds between actin monomers and preventing microfilaments depolymerization. However, the ultraviolet-spectra of interaction between actin and virotoxins is different from that of actin-phallotoxins, suggesting a different molecular interaction. Virotoxins have a more flexible structure when compared with phallotoxins and the presence of two additional hydroxyl groups may provide different reactivity. The intraperitoneal LD50 of virotoxins in mice ranges from 1.0 to 5.1 mg/kg and their main toxicological feature is hemorrhagic hepatic necrosis caused by an interaction of the virotoxins with outer surface of the hepatocyte through unknown mechanisms. At this point, the role of virotoxins in human toxicity remains unclear, although due to its poor oral absorption, little clinical importance is given to this class of toxins.
Poisonous Amanita mushrooms | |||||||||||||||||||||||||||||||||||||
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| Subgenus Amanita |
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| Subgenus Amanitina |
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