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== History ==
== History ==
The toxic properties of death cap mushrooms have been known for most of recorded history, with historical accounts implicating it in the deaths of emperors.<ref>{{cite journal | vauthors = Marmion VJ, Wiedemann TE | title = The death of Claudius | journal = Journal of the Royal Society of Medicine | volume = 95 | issue = 5 | pages = 260–261 | date = May 2002 | pmid = 11983773 | pmc = 1279685 | doi = 10.1177/014107680209500515 }}</ref> Attempts to isolate the toxic compounds began in the late 19th century, with the [[Cytolysis|cytolytic]] elements of [[Amanita phalloides|''A. phalloides'']] being isolated in 1891.<ref>Kobert R (1891) Über Pilzvergiftung. St. Petersburger Med Wochenschr 16:463–471</ref><ref name=":0" /> It has been thought that the Roman Emperor Claudius, in 54 AD, and the Holy Roman Emperor Charles VI, in 1740, were some of the earliest victims of death cap poisoning. Due to this, the death cap mushroom has gained the nickname the ‘killer of kings.’ The beginning of this research into the hemolytic properties of the ''Amanita phalloides'', or the Death Cap Mushroom, began with Eduard Rudolf Kobert in 1891, who originally denoted it ‘phallin,’ and was continued by John Jacob Abel and William Webber Ford in 1908. These mushrooms have been attributed to greater than 90% of all cases of mushroom poisoning, in which no active treatment of intoxication cases currently exists. This mushroom targets mainly the liver, but may also impact the kidneys and central nervous system as well. As a result of the hemolytic and cytolytic properties, this toxin has been considered for anti-tumor treatments in the early 1970s, where the osmotic lysis of cell membranes was hoped to treat the uncontrollable cell division that tumor cells are notorious for. However, in addition to the non-specificity of the toxin, these trials resulted in the development of an increased potassium concentration in the bloodstream due to the extreme intravascular hemolysis and cytolysis of multiple cell types. Due to the discovery of these lethal side effects, this antitumor treatment route was halted to make room for more sophisticated treatment strategies.
The toxic properties of death cap mushrooms have been known for most of recorded history, with historical accounts implicating it in the deaths of emperors.<ref>{{cite journal | vauthors = Marmion VJ, Wiedemann TE | title = The death of Claudius | journal = Journal of the Royal Society of Medicine | volume = 95 | issue = 5 | pages = 260–261 | date = May 2002 | pmid = 11983773 | pmc = 1279685 | doi = 10.1177/014107680209500515 }}</ref> Attempts to isolate the toxic compounds began in the late 19th century, with the [[Cytolysis|cytolytic]] elements of [[Amanita phalloides|''A. phalloides'']] being isolated in 1891.<ref>Kobert R (1891) Über Pilzvergiftung. St. Petersburger Med Wochenschr 16:463–471</ref><ref name=":0" /> It has been thought that the Roman Emperor Claudius, in 54 AD, and the Holy Roman Emperor Charles VI, in 1740, were some of the earliest victims of death cap poisoning. Due to this, the death cap mushroom has gained the nickname the ‘killer of kings.’ The beginning of this research into the hemolytic properties of the ''Amanita phalloides'', or the Death Cap Mushroom, began with Eduard Rudolf Kobert in 1891, who originally denoted it ‘phallin,’ and was continued by John Jacob Abel and William Webber Ford in 1908.<ref>{{Citation |last=Wieland |first=Theodor |title=Phallolysin |date=1986 |url=https://doi.org/10.1007/978-3-642-71295-1_10 |work=Peptides of Poisonous Amanita Mushrooms |pages=207–210 |editor-last=Wieland |editor-first=Theodor |access-date=2023-11-24 |series=Springer Series in Molecular Biology |place=Berlin, Heidelberg |publisher=Springer |language=en |doi=10.1007/978-3-642-71295-1_10 |isbn=978-3-642-71295-1}}</ref> These mushrooms have been attributed to greater than 90% of all cases of mushroom poisoning, in which no active treatment of intoxication cases currently exists. This mushroom targets mainly the liver, but may also impact the kidneys and central nervous system as well.<ref>{{Cite journal |last=Ye |first=Yongzhuang |last2=Liu |first2=Zhenning |date=2018-08-01 |title=Management of Amanita phalloides poisoning: A literature review and update |url=https://www.sciencedirect.com/science/article/pii/S0883944118301862 |journal=Journal of Critical Care |volume=46 |pages=17–22 |doi=10.1016/j.jcrc.2018.03.028 |issn=0883-9441}}</ref> As a result of the hemolytic and cytolytic properties, this toxin has been considered for anti-tumor treatments in the early 1970s, where the osmotic lysis of cell membranes was hoped to treat the uncontrollable cell division that tumor cells are notorious for. However, in addition to the non-specificity of the toxin, these trials resulted in the development of an increased potassium concentration in the bloodstream due to the extreme intravascular hemolysis and cytolysis of multiple cell types. Due to the discovery of these lethal side effects, this antitumor treatment route was halted to make room for more sophisticated treatment strategies.<ref>{{Cite journal |last=Lemaire |first=Mathieu |last2=Halperin |first2=Mitchell L. |date=2009-08 |title=Rapid tumor cell swelling and bursting: beware of collateral damage |url=https://pubmed.ncbi.nlm.nih.gov/19644494/ |journal=Molecular Therapy: The Journal of the American Society of Gene Therapy |volume=17 |issue=8 |pages=1310–1311; author reply 1311–1312 |doi=10.1038/mt.2009.161 |issn=1525-0024 |pmc=2835251 |pmid=19644494}}</ref>


== Physical properties ==
== Physical properties ==

Revision as of 22:30, 24 November 2023

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.[1] It was one of the first toxins discovered in Amanita phalloides when the various toxins in the species where first being researched.[2] The protein itself is observed to come in 3 variations, with observed differences in isoelectric point.[3] 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.

History

The toxic properties of death cap mushrooms have been known for most of recorded history, with historical accounts implicating it in the deaths of emperors.[4] Attempts to isolate the toxic compounds began in the late 19th century, with the cytolytic elements of A. phalloides being isolated in 1891.[5][2] It has been thought that the Roman Emperor Claudius, in 54 AD, and the Holy Roman Emperor Charles VI, in 1740, were some of the earliest victims of death cap poisoning. Due to this, the death cap mushroom has gained the nickname the ‘killer of kings.’ The beginning of this research into the hemolytic properties of the Amanita phalloides, or the Death Cap Mushroom, began with Eduard Rudolf Kobert in 1891, who originally denoted it ‘phallin,’ and was continued by John Jacob Abel and William Webber Ford in 1908.[6] These mushrooms have been attributed to greater than 90% of all cases of mushroom poisoning, in which no active treatment of intoxication cases currently exists. This mushroom targets mainly the liver, but may also impact the kidneys and central nervous system as well.[7] As a result of the hemolytic and cytolytic properties, this toxin has been considered for anti-tumor treatments in the early 1970s, where the osmotic lysis of cell membranes was hoped to treat the uncontrollable cell division that tumor cells are notorious for. However, in addition to the non-specificity of the toxin, these trials resulted in the development of an increased potassium concentration in the bloodstream due to the extreme intravascular hemolysis and cytolysis of multiple cell types. Due to the discovery of these lethal side effects, this antitumor treatment route was halted to make room for more sophisticated treatment strategies.[8]

Physical properties

Phallolysin has three variations, which differ in observed isoelectric point. The variations have differences in the amino acids that make up the protein structure, with identical amounts of some amino acids while varying in others. They have near identical molecular weights of 34 kDa.[1]

Effects on animal cells

Phallolysin has been observed to have hemolytic properties toward a variety of animal cells, with it primarily being observed in mammals. The toxic effects are reduced at higher temperatures.[1][9]

See also

References

  1. ^ a b c Faulstich H, Bühring HJ, Seitz J (September 1983). "Physical properties and function of phallolysin". Biochemistry. 22 (19): 4574–4580. doi:10.1021/bi00288a035. PMID 6626515.
  2. ^ a b Wieland T (1996). "Toxins and Psychoactive Compounds from Mushrooms". In Howard DH, Miller JD (eds.). Human and Animal Relationships. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 229–248. doi:10.1007/978-3-662-10373-9_12. ISBN 978-3-662-10375-3. Retrieved 2022-05-05.
  3. ^ Seeger R (1975-09-01). "Demonstration and isolation of phallolysin, a haemolytic toxin from Amanita phalloides". Naunyn-Schmiedeberg's Archives of Pharmacology. 287 (3): 277–287. doi:10.1007/BF00501473. PMID 1171383. S2CID 20334083.
  4. ^ Marmion VJ, Wiedemann TE (May 2002). "The death of Claudius". Journal of the Royal Society of Medicine. 95 (5): 260–261. doi:10.1177/014107680209500515. PMC 1279685. PMID 11983773.
  5. ^ Kobert R (1891) Über Pilzvergiftung. St. Petersburger Med Wochenschr 16:463–471
  6. ^ Wieland, Theodor (1986), Wieland, Theodor (ed.), "Phallolysin", Peptides of Poisonous Amanita Mushrooms, Springer Series in Molecular Biology, Berlin, Heidelberg: Springer, pp. 207–210, doi:10.1007/978-3-642-71295-1_10, ISBN 978-3-642-71295-1, retrieved 2023-11-24
  7. ^ Ye, Yongzhuang; Liu, Zhenning (2018-08-01). "Management of Amanita phalloides poisoning: A literature review and update". Journal of Critical Care. 46: 17–22. doi:10.1016/j.jcrc.2018.03.028. ISSN 0883-9441.
  8. ^ Lemaire, Mathieu; Halperin, Mitchell L. (2009-08). "Rapid tumor cell swelling and bursting: beware of collateral damage". Molecular Therapy: The Journal of the American Society of Gene Therapy. 17 (8): 1310–1311, author reply 1311–1312. doi:10.1038/mt.2009.161. ISSN 1525-0024. PMC 2835251. PMID 19644494. {{cite journal}}: Check date values in: |date= (help)
  9. ^ Faulstich H, Weckauf-Bloching M (December 1974). "Isolation and toxicity of two cytolytic glycoproteins from Amanita phalloides mushrooms". Hoppe-Seyler's Zeitschrift für Physiologische Chemie. 355 (12): 1489–1494. doi:10.1515/bchm2.1974.355.2.1489. PMID 4461647.
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