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advanced molecular biology The death cap mushroom, Amanita phalloidins, contains

ID: 90691 • Letter: A

Question

advanced molecular biology

The death cap mushroom, Amanita phalloidins, contains several dangerous substances, including the lethal amanitin. This toxin blocks RNA elongation in consumers of the mushroom by binding to eukaryotic RNA polymerase II with very high affinity; it is deadly in concentrations as low as 10^+8 M. The initial reaction to ingestion of the mushroom is gastrointestinal distress (caused by some of the other toxins). These symptoms disappear, but about 48 hours later, the mushroom-eater dies, usually from liver dysfunction. Speculate on why it takes this long for amanitin to kill.

Explanation / Answer

The toxin is adsorbed through the intestinal epithelium and it binds weakly to serum proteins. The liver is the principal organ affected, as it is the first organ encountered after absorption in the gastrointestinal tract. Once in the liver, amanitins are transported by a nonspecific transport system into hepatocytes, producing an extensive centrolobular necrosis. About 60% of absorbed -amanitin is excreted into the bile and is returned to the liver via the enterohepatic circulation. However, other organs, especially the kidney, are susceptible to their toxicity.

Amatoxins are not significantly protein bound and are cleared from plasma within 48h of ingestion. They are filtered by the glomerulus and reabsorbed by the renal tubules, resulting in acute tubular necrosis. Finally, in animal and human post-mortem studies, cellular damage also has been found in the pancreas, adrenal glands, and testes.

Due to progressive decrease in mRNA which leads to deficient protein synthesis, and cell death, the metabolically active tissues dependent on high rates of protein synthesis, such as the cells of the gastrointestinal tract, hepatocytes, and the proximal convoluted tubules of kidney, are disproportionately affected.