Amatoxin
Encyclopedia
Amatoxins are a subgroup of at least eight toxic
compounds found in several genera of poisonous mushrooms, most notably Amanita phalloides and several other members of the genus Amanita
, as well as some Conocybe
, Galerina
and Lepiota
mushroom species.
and Rudolf Hallermayer of the University of Munich
. All amatoxins are oligopeptides that are synthesized as 35-amino-acids-long proproteins
, from which the final eight amino acids are cleaved by a prolyl oligopeptidase.
There are currently ten known amatoxins:
δ-Amanitin has been reported, but its chemical structure has not been determined.
, a vital enzyme in the synthesis of messenger RNA
(mRNA), microRNA, and small nuclear RNA (snRNA). Without mRNA, essential protein synthesis
, and hence cell metabolism, grind to a halt and the cell dies.
is the principal organ affected, as it is the organ which is first encountered after absorption in the gastrointestinal tract
, though other organs, especially the kidney
s, are susceptible. The RNA polymerase of Amanita phalloides is insensitive to the effects of amatoxins; thus, the mushroom does not poison itself.
The estimated minimum lethal dose is 0.1 mg/kg or 7 mg 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 a severe hepatorenal syndrome
.
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.
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
compounds found in several genera of poisonous mushrooms, most notably Amanita phalloides and several other members of the genus Amanita
Amanita
The genus Amanita contains about 600 species of agarics including some of the most toxic known mushrooms found worldwide. This genus is responsible for approximately 95% of the fatalities resulting from mushroom poisoning, with the death cap accounting for about 50% on its own...
, as well as some Conocybe
Conocybe
The genus Conocybe is a genus of mushrooms consisting of Conocybe tenera and at least 243 other species, with at least 50 species in North America....
, Galerina
Galerina
Galerina is a genus of small brown-spored saprobic mushrooms, with over 300 species found throughout the world, from the far north to remote Macquarie Island in the Southern Ocean. Species are typically small and hygrophanous, with a slender and brittle stem. They are often found growing on wood,...
and Lepiota
Lepiota
Lepiota is a genus of gilled mushrooms in the family Agaricaceae. All Lepiota species are ground-dwelling saprotrophs with a preference for rich, calcareous soils. Basidiocarps are agaricoid with whitish spores, typically with scaly caps and a ring on the stem. Around 400 species of Lepiota are...
mushroom species.
Structure
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. WielandHeinrich Otto Wieland
Heinrich Otto Wieland was a German chemist. He won the 1927 Nobel Prize in Chemistry for his research into the bile acids. In 1901 Wieland received his doctorate at the University of Munich while studying under Johannes Thiele...
and Rudolf Hallermayer of the University of Munich
Ludwig Maximilians University of Munich
The Ludwig Maximilian University of Munich , commonly known as the University of Munich or LMU, is a university in Munich, Germany...
. All amatoxins are oligopeptides that are synthesized as 35-amino-acids-long proproteins
Protein precursor
A protein precursor, also called a pro-protein or pro-peptide, is an inactive protein that can be turned into an active form by posttranslational modification. The name of the precursor for a protein is often prefixed by pro...
, from which the final eight amino acids are cleaved by a prolyl oligopeptidase.
| Name | R1 | R2 | R3 | R4 | R5 |
|---|---|---|---|---|---|
| α-Amanitin Alpha-amanitin alpha-Amanitin or α-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 Amanita genus of mushrooms, one being the Death cap as well as the Destroying angel, a complex of similar species, principally A.... |
OH | OH | NH2 | OH | OH |
| β-Amanitin Beta-amanitin beta-Amanitin or β-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 Amanita genus of mushrooms, one being the Death cap as well as the Destroying angel, a complex of similar species, principally A. virosa... |
OH | OH | OH | OH | OH |
| γ-Amanitin Gamma-amanitin gamma-Amanitin or γ-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 Amanita genus of mushrooms, one being the Death cap as well as the Destroying angel, a complex of similar species, principally... |
H | OH | NH2 | OH | OH |
| ε-Amanitin Epsilon-Amanitin epsilon-Amanitin or ε-amanitin is a cyclic peptide. It is an amatoxin, all of which are found in several members of the Amanita genus of mushrooms. The oral of ε-amanitin is approximately 0.1 mg/kg.-Toxicology:... |
H | OH | OH | OH | OH |
| Amanullin Amanullin Amanullin is a cyclic nonribosomal peptide. It is an amatoxin, all of which are found in several members of the Amanita genus of mushrooms. The oral of amanullin is approximately 20 mg/kg in mice, however it is non-toxic in humans.-Toxicology:... |
H | H | NH2 | OH | OH |
| Amanullinic acid Amanullinic acid Amanullinic acid is a cyclic nonribosomal peptide. It is an amatoxin, all of which are found in several members of the Amanita genus of mushrooms. The oral of amanullinic acid is approximately 0.1 mg/kg in mice.-External links:*... |
H | H | OH | OH | OH |
| Amaninamide Amaninamide Amaninamide is a cyclic nonribosomal peptide. It is one of the amatoxins, all of which are found in several members of the Amanita genus of mushrooms.-Toxicology:Like other amatoxins, amaninamide is an inhibitor of RNA polymerase II... |
OH | OH | NH2 | H | OH |
| Amanin Amanin Amanin is a cyclic peptide. It is one of the amatoxins, all of which are found in several members of the Amanita genus of mushrooms.-Toxicology:Like other amatoxins, amanin is an inhibitor of RNA polymerase II... |
OH | OH | OH | H | OH |
| Proamanullin Proamanullin Promanullin is a cyclic nonribosomal peptide. It is an amatoxin, all of which are found in several members of the Amanita genus of mushrooms.-Toxicology:... |
H | H | NH2 | OH | H |
δ-Amanitin has been reported, but its chemical structure has not been determined.
Mechanism
Their major toxic mechanism is the inhibition of RNA polymerase IIRNA polymerase II
RNA polymerase II is an enzyme found in eukaryotic cells. It catalyzes the transcription of DNA to synthesize precursors of mRNA and most snRNA and microRNA. A 550 kDa complex of 12 subunits, RNAP II is the most studied type of RNA polymerase...
, a vital enzyme in the synthesis of messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
(mRNA), microRNA, and small nuclear RNA (snRNA). Without mRNA, essential protein synthesis
Protein biosynthesis
Protein biosynthesis is the process in which cells build or manufacture proteins. The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription of nuclear DNA into messenger RNA, which is then...
, and hence cell metabolism, grind to a halt and the cell dies.
Clinical symptoms
The liverLiver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
is the principal organ affected, as it is the organ which is first encountered after absorption in the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....
, though other organs, especially the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s, are susceptible. The RNA polymerase of Amanita phalloides is insensitive to the effects of amatoxins; thus, the mushroom does not poison itself.
The estimated minimum lethal dose is 0.1 mg/kg or 7 mg of toxin in adults. Their swift intestinal absorption coupled with their thermostability
Thermostability
Thermostability is the quality of a substance to resist irreversible change in its chemical or physical structure at a high relative temperature.Thermostable materials may be used industrially as fire retardants...
leads to rapid development of toxic effects in a relatively short period of time. The most severe effects are toxic hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
with centrolobular necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
and hepatic steatosis, as well as acute tubulointerstitial nephropathy
Nephropathy
Nephropathy refers to damage to or disease of the kidney. An older term for this is nephrosis.-Causes:Causes of nephropathy include administration of analgesics, xanthine oxidase deficiency, and long-term exposure to lead or its salts...
, which altogether induce a severe hepatorenal syndrome
Hepatorenal syndrome
Hepatorenal syndrome is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure...
.
Treatment
Treatment involves high dose penicillinPenicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....
as well as supportive care in cases of hepatic and renal injury. Silibinin
Silibinin
Silibinin , also known as silybin, is the major active constituent of silymarin, standardized extract of the milk thistle seeds, containing mixture of flavonolignans consisting of among others of silibinin, isosilibinin, silicristin and silidianin. Silibinin itself is mixture of two diastereomers...
, a product found in milk thistle
Milk thistle
The milk thistle is a thistle of the genus Silybum Adans., a flowering plant of the daisy family . They are native to the Mediterranean regions of Europe, North Africa and the Middle East...
, 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
Hepatorenal syndrome
Hepatorenal syndrome is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure...
has developed the prognosis is guarded at best.