Amatoxin

Last updated

Amatoxin is the collective name of a subgroup of at least nine related toxic compounds found in three genera of poisonous mushrooms ( Amanita , Galerina and Lepiota ) and one species of the genus Pholiotina . [1] Amatoxins are very potent, as little as half a mushroom cap can cause severe liver injury if swallowed.

Contents

Structure

The backbone structure (black) is the same in all the amatoxins and five variable groups (red) determine the specific compound. Amatoxins generic strucuture.png
The backbone structure (black) is the same in all the amatoxins and five variable groups (red) determine the specific compound.

The compounds have a similar structure, that of eight amino-acid residues arranged in a conserved macrobicyclic motif (an overall pentacyclic structure when counting the rings inherent in the proline and tryptophan-derived residues); they were isolated in 1941 by Heinrich O. Wieland and Rudolf Hallermayer. [2] All amatoxins are cyclic peptides that are synthesized as 35-amino-acid proproteins, from which the final eight amino acids are cleaved by a prolyl oligopeptidase. [3] The schematic amino acid sequence of amatoxins is Ile-Trp-Gly-Ile-Gly-Cys-Asn-Pro with cross-linking between Trp and Cys via the sulfoxide (S=O) moiety and hydroxylation in variants of the molecule; enzymes for these processings steps remain unknown.

There are currently ten named amatoxins: [4]

NameR1R2R3R4R5
α-Amanitin OHOHNH2OHOH
β-Amanitin OHOHOHOHOH
γ-Amanitin OHHNH2OHOH
ε-Amanitin OHHOHOHOH
Amanullin HHNH2OHOH
Amanullinic acid HHOHOHOH
Amaninamide OHOHNH2HOH
Amanin OHOHOHHOH
Proamanullin HHNH2OHH

δ-Amanitin has been reported, but its chemical structure has not been determined.

Family relations

Amanitin/phalloidin precursor
Identifiers
SymbolAmanitin/phalloidin
InterPro IPR027582

Amanitin is very closely related to phalloidins, which are bicyclic 7-residue toxins. They both are part of the MSDIN protein family, so named after the highly conserved 5-amino-acid sequence in the preproteins. A 2014 research study determined that there exists a significant number of uncharacterized MSDIN sequences in Amanita genomes. [5]

Mechanism

Amatoxins are potent and selective inhibitors of RNA polymerase II, a vital enzyme in the synthesis of messenger RNA (mRNA), microRNA, and small nuclear RNA (snRNA). Without mRNA, which is the template for protein synthesis, cell metabolism stops and apoptosis ensues. [6] The RNA polymerase of Amanita phalloides has mutations that make it insensitive to the effects of amatoxins; thus, the mushroom does not poison itself. [7]

Amatoxins are able to travel through the bloodstream to reach the organs in the body. While these compounds can damage many organs, damage to the liver and heart result in fatalities. At the molecular level, amatoxins cause damage to cells of these organs by causing perforations in the plasma membranes resulting in misplaced organelles that are normally in the cytoplasm to be found in the extracellular matrix. [8] beta-Amanitin is also an inhibitor of eukaryotic RNA polymerase II and RNA polymerase III, and as a result, mammalian protein synthesis. It has not been found to inhibit RNA polymerase I or bacterial RNA polymerase. [9] Because it inactivates the RNA polymerases, the liver is unable to repair damage and the cells of the liver die off quickly. [10]

a-Amanitin (red) bound to RNA polymerase II from Saccharomyces cerevisiae (brewer's yeast). From PDB: 1K83 . Alpha-Amanitin-RNA polymerase II complex 1K83.png
α-Amanitin (red) bound to RNA polymerase II from Saccharomyces cerevisiae (brewer's yeast). From PDB: 1K83 ​.

Alpha-amanitin (α-Amanitin) primarily affects the bridge helix of the RNA pol II complex, a highly conserved domain 35 amino acids long. At the N-terminus and the C-terminus of this region there are hinge structures that undergo significant conformational changes throughout the nucleotide addition cycle, and are essential for its progression. [12] One of the many roles of the bridge helix is facilitating the translocation of DNA. [13] Alpha-amanitin binds to the bridge helix of the RNA Pol II complex and it also binds to part of the complex that is adjacent to the bridge helix, while it is in one specific conformation. This binding locks the bridge helix into place, dramatically slowing its movement in translocating the DNA. [11] The rate of pol II translocation of DNA is reduced from several thousand to a few nucleotides per minute. [14] [15]

Symptoms of exposure

Upon exposure to amatoxins, the liver is the principal organ affected as it is the organ which is first encountered after absorption in the gastrointestinal tract. There is no evidence that amatoxins are absorbed through skin. One study done on mice shows that alpha-Amanitin is not absorbed through skin and therefore cannot have any toxic effects. [16] More specifically, exposure to amatoxins may cause irritation of the respiratory tract, headache, dizziness, nausea, shortness of breath, coughing, insomnia, diarrhea, gastrointestinal disturbances, back pain, urinary frequency, liver and kidney damage, or death if ingested or inhaled. For β-amanitin, there has been no full toxicological study. However, safety data sheets indicate that if it comes in contact with skin, it may cause irritation, burns, redness, severe pain, and could be absorbed through the skin, causing similar effects to exposure via inhalation and ingestion. Contact with the eyes may result in irritation, corneal burns, and eye damage. [17] Persons with pre-existing skin, eye, or central nervous systems disorders, impaired liver, kidney, or pulmonary function may be more susceptible to the effects of this substance.

Amatoxin poisoning shows a biphasic clinical pattern. An initial (12–24 hours) period of acute symptoms is followed by a period of relative wellness that lasts for 12–24 hours. After this period, liver and kidney failure supervene with death typically occurring from day 2 onwards.[ citation needed ]

The estimated minimum lethal dose is 0.1 mg/kg or 7  to 10 milligrams of toxin in adults. Their swift intestinal absorption coupled with their thermostability leads to rapid development of toxic effects in a relatively short period of time. The most severe effects are toxic hepatitis with centrolobular necrosis and hepatic steatosis, as well as acute tubulointerstitial nephropathy, which altogether induce severe liver failure and kidney failure.

Treatment

There are many anecdotal and partially-studied treatments in use worldwide. One study in mice showed null results for all studied treatments. Treatments showing no discernable value included N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin. [18]

Treatment involves high-dose penicillin as well as supportive care in cases of hepatic and renal injury. Silibinin, a product found in milk thistle, is a potential antidote to amatoxin poisoning, although more data needs to be collected. Cautious attention is given to maintaining hemodynamic stability, although if hepatorenal syndrome has developed the prognosis is guarded at best. [19]

Detection

Presence of amatoxins in mushroom samples may be detected by the Meixner test (also known as the Wieland test). The amatoxins may be quantitated in plasma or urine using chromatographic techniques to confirm a diagnosis of poisoning in hospitalized patients and in postmortem tissues to aid in a medicolegal investigation of a suspected fatal overdosage. [20]

In 2020, a monoclonal antibody-based lateral flow immunoassay has been developed that can quickly and selectively detect amatoxins. [21] [22] This test sensitively detects alpha-amanitin and gamma-amanitin (clearly detects 10 ng/mL), and exhibits slightly less detection for beta-amanitin (0.5% cross-reactivity; 2000 ng/mL). Although this test cross-reacts with phallotoxins at 0.005% (200,000 ng/mL), the phallotoxins would not interfere in urine sampling and there are very rare instances where a mushroom produces phallotoxins without producing amatoxins.

Studies

In a 2013 study on the toxin concentration in Amanita phalloides all parts of the mushroom were found to contain amatoxins and it was determined that the highest concentrations were found in the gills and cap with the lowest levels in the spores and mycelium. [23] An additional study published in 2013 by many of the same authors found no difference in the ITS sequence of Amanita phalloides var. alba but did find different concentrations of toxins. [24] The gills and cap of Amanita phalloides var. alba also contained the highest level with very low levels noted in the spores, volva and stipe however in this variant the spores had a higher concentration of all toxins besides gamma amanitin than was found in Amanita phalloides. The spores of Amanita phalloides var. alba contained 0.89 mg/g of alpha-amanitin, 0.48 mg/g of beta-amanitin and 0.001 mg/g gamma-amanitin in contrast to the 2.46, 1.94 and 0.36 mg/g found in the gills and the 2.40, 1.75 and 0.27 mg/g found in the cap. The concentration found in the gills, cap, stipe and volva of Amanita phalloides var. alba is lower than in Amanita phalloides however the spores were shown to contain a higher concentration. [24] In both studies six mushrooms were spore printed, dried and tested with the toxin level in the whole mushroom being derived from testing one half of the whole mushroom cut down the middle, the other half was divided into cap, gill, stipe and volva sections to test individually with the parts ground into a powder and tested as 1gram samples. [23] [24] In 2010 a study on Amanita bisporigera , the destroying angel, determined that the concentrations of toxins in the spores were also lower than the levels found in the cap or stipe. [25]

Toxin concentration in Amanita phalloides (mg/g) [23]
ToxinCapGillsStipeVolvaSporesWhole dry mushroomWhole fresh mushroomMycelium
Alpha-amanitin2.953.392.361.030.0872.800.330.024
Beta-amanitin2.532.951.750.640.0482.380.280.01
Gamma-amanitin0.620.660.50.250.180.60.070.24
Phallacidin2.272.062.041.880.0552.120.250.42
Phalloidin1.401.381.181.250.0181.320.150.01
Toxin concentration in Amanita phalloides var. alba (mg/g) [24]
ToxinCapGillsStipeVolvaSporesWhole dry mushroomWhole fresh mushroom
Alpha-amanitin2.402.461.520.560.892.140.21
Beta-amanitin1.751.941.000.360.481.710.16
Gamma-amanitin0.270.360.210.070.0010.310.03
Phallacidin1.642.262.062.080.992.100.20
Phalloidin0.871.301.131.340.121.090.10
Toxin concentration in Amanita bisporigera (mg/g) [25]
ToxinCapStipeSpores
Alpha-amanitin1.70 ± 0.681.70 ± 0.450.30 ± 0.04
Phallacidin2.71 ± 0.651.66 ± 0.400.02 ± 0.01
Phalloidin11.98 ± 1.6611.15 ± 2.430.00 ± 0.05

Amatoxins are extremely toxic to humans with Amanita phalloides and its variants making up many of the cases of fatal toxicity after consumption.These toxins have high heat stability and this property combined with their solubility in water make them exceptionally toxic as they are not destroyed by cooking or drying. [26] In addition, amatoxins are resistant to enzyme and acid degradation, and therefore when ingested they are not inactivated in the gastrointestinal tract. [26] A fatal case was reported after consuming A. phalloides that had been frozen for 7–8 months, thus demonstrating that these compounds are also resistant to the freeze/thawing processes. [26] Additionally, amatoxins decompose very slowly when stored in open, aqueous solutions or following prolonged exposure to sun or neon light. [26]

In 2015 a case study was conducted on a patient who cooked and consumed just the caps from two Amanita phalloides mushrooms and was subsequently admitted to hospital a day later. The subject was a 61 year old man with a body weight of 67kg who was presenting with fatigue, abdominal pain, nausea, vomiting and diarrhea. Mushrooms were collected from the same region and shown to the patient in order to confirm that these were what he had eaten and two mushrooms of approximately the same size and level of maturity were selected for study. [27] Previous studies have demonstrated that younger mushrooms can contain a higher concentration of toxins than is found in mature specimens. [28] The combined weight of the caps of these two mushrooms was 43.4g fresh or 4.3g when dry and when tested were found to contain a total of 21.3mg of amatoxin distributed as 11.9mg alpha-amanitin, 8.4mg beta-amanitin and 1mg gamma-amanitin. Analysis of the patient's urine after 4 days of treatment in hospital showed a concentration of 2.7ng/ml alpha-amanitin and 1.25ng/ml beta-amanitin with no gamma-amanitin detected. The patient survived and was discharged after 9 days of treatment with follow up tests showing no signs of liver damage but based on this case it was estimated that an oral dose of 0.32mg amatoxin per kg of body mass could be lethal with an approximate lethal dose of alpha-amanitin being 0.2mg/kg when taken orally. It was estimated that consuming more than 50g of fresh Amanita phalloides, roughly 2 medium sized mushrooms could be deadly. Clinical tests showed that the amount consumed by the patient remained below the hypothetical lethal dose, which the study notes probably varies depending on patient health, predisposition to liver damage and regional variation in toxin concentrations. [27]

Anecdotes have been repeated in field guides that claim foragers have fallen ill from spores alone after collecting toxic Amanita species in the same basket, unwittingly leaving their spores to collect on the harvest before the toxic ones were discarded. This subject however has not been researched and studies make no claims one way or the other as to the possibility of poisoning from spores alone. Given that the concentration of toxins found in the spores is lower than that of the cap it would require the consumption of a substantial mass of spores in excess of the weight of the mushroom caps themselves, in order to reach a fatal dose.

Mushroom species

Amatoxin-containing mushroom species from the genera Amanita, Galerina and Lepiota. [29] [30]

Amanita species Galerina species Lepiota species
Amanita phalloides Galerina badipes Lepiota brunneoincarnata
Amanita bisporigera Galerina beinrothii Lepiota brunneolilacea
Amanita decipiens Galerina fasciculata Lepiota castanea
Amanita hygroscopica Galerina helvoliceps Lepiota clypeolaria
Amanita ocreata Galerina marginata Lepiota clypeolarioides
Amanita suballiacea Galerina sulciceps Lepiota felina
Amanita tenuifolia Galerina unicolor Lepiota fulvella
Amanita verna Galerina venenata Lepiota fuscovinacea
Amanita virosa Lepiota griseovirens
Lepiota heimii
Lepiota helveoloides
Lepiota kuehneri
Lepiota langei
Lepiota lilacea
Lepiota locanensis
Lepiota ochraceofulva
Lepiota pseudohelveola
Lepiota pseudolilacea
Lepiota rufescens
Lepiota subincarnata
Lepiota xanthophylla

See also

Related Research Articles

<i>Amanita phalloides</i> Poisonous mushroom (death cap)

Amanita phalloides, commonly known as the death cap, is a deadly poisonous basidiomycete fungus, one of many in the genus Amanita. Widely distributed across Europe, but 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.

<span class="mw-page-title-main">Destroying angel</span> Deadly poisonous fungus

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.

α-Amanitin Chemical compound

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 and Conocybe filaris. The oral LD50 of amanitin is 100 μg/kg for rats.

<span class="mw-page-title-main">Oligopeptide</span>

An oligopeptide, often just called peptide, consists of two to twenty amino acids and can include dipeptides, tripeptides, tetrapeptides, and pentapeptides. Some of the major classes of naturally occurring oligopeptides include aeruginosins, cyanopeptolins, microcystins, microviridins, microginins, anabaenopeptins, and cyclamides. Microcystins are best studied, because of their potential toxicity impact in drinking water. A review of some oligopeptides found that the largest class are the cyanopeptolins (40.1%), followed by microcystins (13.4%).

<span class="mw-page-title-main">Mushroom poisoning</span> Harmful effects from ingestion of toxic substances present in a mushroom

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.

<i>Amanita virosa</i> Species of fungus

Amanita virosa, commonly known in Europe as the destroying angel or the European destroying angel amanita, is a deadly poisonous basidiomycete fungus, one of many in the genus Amanita. Occurring in Europe, A. virosa associates with various deciduous and coniferous trees. The large fruiting bodies appear in summer and autumn; the caps, stipes and gills are all white in colour.

<i>Amanita verna</i> Species of fungus

Amanita verna, commonly known as the fool's mushroom or the spring destroying angel, is a deadly poisonous basidiomycete fungus, one of many in the genus Amanita. Occurring in Europe in spring, A. verna associates with various deciduous and coniferous trees. The caps, stipes and gills are all white in colour.

<i>Galerina marginata</i> Poisonous fungus in the family Hymenogastraceae

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.

<i>Amanita ocreata</i> Species of poisonous fungus in the genus Amanita

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.

β-Amanitin Cyclic peptide part of a group of toxins present in Amanita mushrooms

β-Amanitin (beta-Amanitin) is a cyclic peptide comprising eight amino acids. It is part of a group of toxins called amatoxins, which can be found in several mushrooms belonging to the genus Amanita. Some examples are the death cap and members of the destroying angel complex, which includes A. virosa and A. bisporigera. Due to the presence of α-Amanitin, β-Amanitin, γ-Amanitin and epsilon-Amanitin these mushrooms are highly lethal to human beings.

γ-Amanitin Cyclic peptide part of a group of toxins present in Amanita mushrooms

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.

The phallotoxins consist of at least seven compounds, all of which are bicyclic heptapeptides, 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.

<span class="mw-page-title-main">Phallolysin</span>

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.

<span class="mw-page-title-main">Amaninamide</span> Chemical compound

Amaninamide is a cyclic peptide. It is one of the amatoxins, all of which are found in several members of the mushroom genera Amanita, Lepiota and Galerina. It differs from alpha-amanitin in lacking the hydroxyl group on tryptophan. This alters its UV absorption spectrum but not its toxicity.

<i>Galerina sulciceps</i> Species of fungus

Galerina sulciceps is a dangerously toxic species of fungus in the family Strophariaceae, of the order Agaricales. It is distributed in tropical Indonesia and India, but has reportedly been found fruiting in European greenhouses on occasion. More toxic than the deathcap, G. sulciceps has been shown to contain the toxins alpha- (α-), beta- (β-) and gamma- (γ-) amanitin; a series of poisonings in Indonesia in the 1930s resulted in 14 deaths from the consumption of this species. It has a typical "little brown mushroom" appearance, with few obvious external characteristics to help distinguish it from many other similar nondescript brown species. The fruit bodies of the fungus are tawny to ochre, deepening to reddish-brown at the base of the stem. The gills are well-separated, and there is no ring present on the stem.

<i>Amanita bisporigera</i> Poisonous species of fungus in the family Amanitaceae endemic to North America

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.

<i>Amanita exitialis</i> Species of fungus

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.

<i>Amanita sphaerobulbosa</i> Species of fungus

Amanita sphaerobulbosa, commonly known as the Asian abrupt-bulbed Lepidella, is a species of agaric fungus in the family Amanitaceae. First described by mycologist Tsuguo Hongo in 1969, it is found in Southern Asia.

<i>Amanita fuliginea</i> Species of fungus

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.

Amanita hygroscopia, also known as the pink-gilled destroying angel is a deadly poisonous fungus, one of many in the genus Amanita.

References

  1. ↑ Diaz JH (March 2018). "Amatoxin-Containing Mushroom Poisonings: Species, Toxidromes, Treatments, and Outcomes". Wilderness & Environmental Medicine. 29 (1): 111–118. doi: 10.1016/j.wem.2017.10.002 . PMID   29325729.
  2. ↑ Litten W (March 1975). "The most poisonous mushrooms". Scientific American. 232 (3): 90–101. Bibcode:1975SciAm.232c..90L. doi:10.1038/scientificamerican0375-90. PMID   1114308.
  3. ↑ Hallen HE, Luo H, Scott-Craig JS, Walton JD (November 2007). "Gene family encoding the major toxins of lethal Amanita mushrooms". Proceedings of the National Academy of Sciences of the United States of America. 104 (48): 19097–19101. Bibcode:2007PNAS..10419097H. doi: 10.1073/pnas.0707340104 . PMC   2141914 . PMID   18025465.
  4. ↑ Baumann K, Münter K, Faulstich H (April 1993). "Identification of structural features involved in binding of alpha-amanitin to a monoclonal antibody". Biochemistry. 32 (15): 4043–4050. doi:10.1021/bi00066a027. PMID   8471612.
  5. ↑ Li P, Deng W, Li T (June 2014). "The molecular diversity of toxin gene families in lethal Amanita mushrooms". Toxicon. 83: 59–68. doi:10.1016/j.toxicon.2014.02.020. PMID   24613547.
  6. ↑ Karlson-Stiber C, Persson H (September 2003). "Cytotoxic fungi--an overview". Toxicon. 42 (4): 339–349. doi:10.1016/S0041-0101(03)00238-1. PMID   14505933.
  7. ↑ Horgen PA, Vaisius AC, Ammirati JF (September 1978). "The insensitivity of mushroom nuclear RNA polymerase activity to inhibition by amatoxins". Archives of Microbiology. 118 (3): 317–319. Bibcode:1978ArMic.118..317H. doi:10.1007/BF00429124. PMID   567964. S2CID   37127957.
  8. ↑ Meldolesi J, Pelosi G, Brunelli A, Genovese E (June 1967). "Electron microscopic studies on the effects of amanitin in mice: liver and heart lesions". Virchows Archiv für Pathologische Anatomie und Physiologie und für Klinische Medizin. 342 (3): 221–235. doi:10.1007/bf00960591. PMID   5301504. S2CID   12556291.
  9. ↑ "β-Amanitin from Amanita phalloides". Sigma-Aldrich. Retrieved 12 March 2013.
  10. ↑ "Polypeptide Toxins in Amanita Mushrooms". Cornell University . Retrieved 12 March 2013.
  11. 1 2 Bushnell DA, Cramer P, Kornberg RD (February 2002). "Structural basis of transcription: alpha-amanitin-RNA polymerase II cocrystal at 2.8 A resolution". Proceedings of the National Academy of Sciences of the United States of America. 99 (3): 1218–1222. Bibcode:2002PNAS...99.1218B. doi: 10.1073/pnas.251664698 . PMC   122170 . PMID   11805306.
  12. ↑ Weinzierl RO (Sep 2011). "The Bridge Helix of RNA polymerase acts as a central nanomechanical switchboard for coordinating catalysis and substrate movement". Archaea. 2011: 608385. doi: 10.1155/2011/608385 . PMC   3270539 . PMID   22312317.
  13. ↑ Hein PP, Landick R (November 2010). "The bridge helix coordinates movements of modules in RNA polymerase". BMC Biology. 8: 141. doi: 10.1186/1741-7007-8-141 . PMC   2993669 . PMID   21114873.
  14. ↑ Chafin DR, Guo H, Price DH (August 1995). "Action of alpha-amanitin during pyrophosphorolysis and elongation by RNA polymerase II". The Journal of Biological Chemistry. 270 (32): 19114–19119. doi: 10.1074/jbc.270.32.19114 . PMID   7642577.
  15. ↑ Rudd MD, Luse DS (August 1996). "Amanitin greatly reduces the rate of transcription by RNA polymerase II ternary complexes but fails to inhibit some transcript cleavage modes". The Journal of Biological Chemistry. 271 (35): 21549–21558. doi: 10.1074/jbc.271.35.21549 . PMID   8702941.
  16. ↑ Kaya E, Surmen MG, Yaykasli KO, Karahan S, Oktay M, Turan H, et al. (June 2014). "Dermal absorption and toxicity of alpha amanitin in mice". Cutaneous and Ocular Toxicology. 33 (2): 154–160. doi:10.3109/15569527.2013.802697. PMID   23763309. S2CID   32405244.
  17. ↑ "β-Amanitin from Amanita phalloides". Safety Data Sheet. Sigma-Aldrich. Catalog number A1304. Retrieved 2021-05-11.
  18. ↑ Tong TC, Hernandez M, Richardson WH, Betten DP, Favata M, Riffenburgh RH, et al. (September 2007). "Comparative treatment of alpha-amanitin poisoning with N-acetylcysteine, benzylpenicillin, cimetidine, thioctic acid, and silybin in a murine model". Annals of Emergency Medicine. 50 (3): 282–288. doi:10.1016/j.annemergmed.2006.12.015. PMID   17559970.
  19. ↑ Piqueras J (February 1989). "Hepatotoxic mushroom poisoning: diagnosis and management". Mycopathologia. 105 (2): 99–110. doi:10.1007/bf00444032. PMID   2664527. S2CID   29687288.
  20. ↑ Baselt R (2008). Disposition of Toxic Drugs and Chemicals in Man (8th ed.). Foster City, CA: Biomedical Publications. pp. 52–54.
  21. ↑ Bever CS, Adams CA, Hnasko RM, Cheng LW, Stanker LH (2020-04-17). "Lateral flow immunoassay (LFIA) for the detection of lethal amatoxins from mushrooms". PLOS ONE. 15 (4): e0231781. Bibcode:2020PLoSO..1531781B. doi: 10.1371/journal.pone.0231781 . PMC   7164595 . PMID   32302363.
  22. ↑ Bever CS, Swanson KD, Hamelin EI, Filigenzi M, Poppenga RH, Kaae J, et al. (February 2020). "Rapid, Sensitive, and Accurate Point-of-Care Detection of Lethal Amatoxins in Urine". Toxins. 12 (2): 123. doi: 10.3390/toxins12020123 . PMC   7076753 . PMID   32075251.
  23. 1 2 3 Kaya E, Karahan S, Bayram R, Yaykasli KO, Colakoglu S, Saritas A (December 2015). "Amatoxin and phallotoxin concentration in Amanita phalloides spores and tissues". Toxicology and Industrial Health. 31 (12): 1172–1177. Bibcode:2015ToxIH..31.1172K. doi:10.1177/0748233713491809. PMID   23719849. S2CID   206543780.
  24. 1 2 3 4 Kaya E, Yilmaz I, Sinirlioglu ZA, Karahan S, Bayram R, Yaykasli KO, et al. (December 2013). "Amanitin and phallotoxin concentration in Amanita phalloides var. alba mushroom". Toxicon. 76: 225–233. doi:10.1016/j.toxicon.2013.10.008. PMID   24139877.
  25. 1 2 Mcknight TA, Mcknight KB, Skeels MC (2010). "Amatoxin and phallotoxin concentration in amanita bisporigera spores". Mycologia. 102 (4): 763–765. doi:10.3852/09-131. PMID   20648744. S2CID   29289507.
  26. 1 2 3 4 Garcia J, Costa VM, Carvalho A, Baptista P, de Pinho PG, de Lourdes Bastos M, Carvalho F (December 2015). "Amanita phalloides poisoning: Mechanisms of toxicity and treatment". Food and Chemical Toxicology. 86: 41–55. doi:10.1016/j.fct.2015.09.008. hdl: 10198/17717 . PMID   26375431.
  27. 1 2 Yilmaz I, Ermis F, Akata I, Kaya E (December 2015). "A Case Study: What Doses of Amanita phalloides and Amatoxins Are Lethal to Humans?". Wilderness & Environmental Medicine. 26 (4): 491–496. doi: 10.1016/j.wem.2015.08.002 . PMID   26453489.
  28. ↑ Vetter J (January 1998). "Toxins of Amanita phalloides". Toxicon. 36 (1): 13–24. doi:10.1016/S0041-0101(97)00074-3. PMID   9604278.
  29. ↑ Enjalbert F, Rapior S, Nouguier-Soulé J, Guillon S, Amouroux N, Cabot C (26 November 2002). "Treatment of amatoxin poisoning: 20-year retrospective analysis". Journal of Toxicology. Clinical Toxicology. 40 (6): 715–757. doi:10.1081/CLT-120014646. PMID   12475187. S2CID   22919515.
  30. ↑ Walton J (9 May 2018). The cyclic peptide toxins of Amanita and other poisonous mushrooms. Cham, Switzerland: Springer. ISBN   978-3-319-76822-9. OCLC   1035556400.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.