Amanitins

Cephaeline occurs in the ground roots of ipecac along with emetine. The Brazilian variety usually contains about 0.5% 

Crystalline solid, obtained as needles from ether faintly bitter in taste melts at 115°C (239°F) insoluble in water, dissolves in organic solvents and dilute mineral acids. 

The toxicity of cephaeline is lower than that of emetine. The toxic effects are cumulative. Ingestion of high doses may produce hypotension, muscle weakness, and gastrointestinal problems, including nausea, vomiting, and diarrhea. 

Among the highly toxic species of mushrooms are the Amanita species. The group of amanitin alkaloids present in Amanita phalloides are a-, and y-amanitins and amanin. The former two types of alkaloids occur to the extent of 4-5 mg/100 g. The structure of a- and /1-amanitin is as follows  

Amanitins are highly toxic alkaloids. The fatal dose for humans is about 0.1 mg/kg. The delayed toxic effects begin about 

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Ph The phenyl group, CfiHs-. pH See hydrogen-ion concentration, phaeophorbide See chlorophyll, phaeophytin See chlorophyll, phalloidins See amanitins. 

Form of RNA Polymerase Sensitivity to ct-Amanitin Major Products... 

One peptide toxin from the mushroom Amanita phalhides, a-amanitin, is a specific differential inhibitor of the eukaryotic nuclear DNA-dependent RNA polymerases and as such has proved to be a powerful research tool (Table 37-2). a-Amanitin blocks the translocation of RNA polymerase during transcription. 

Scheme 4 u-Amanitin. Standard three letter abbreviations are used for the amino acids... 

Falchuk, K.H., B. Mazus, E. Ber, L. Ulpino-Lobb, and B.L. Vallee. 1985. Zinc deficiency and the Euglena gracilis chromatin formation of an a-amanitin-resistant RNA polymerase II. Biochemistry 24 2576-2580. 

Mushroom-Aman/fa pf7a//o/des Amanitins - peptide-based toxins 200... 

Amino acid with antidysiipidemic and antihypergiycemic activities Amanitins - toxic peptides... 

H Fungi - Amanita phalloides and Agaricus phalloides Cyanobacteria -Lyngbya majuscula Phalloidin, phallicidin, and amanitin - toxic peptides Majusculamide D - cytotoxic peptide Microcolin A - peptide with immunosuppressive, antileukemic and protein kinase C inhibitory activity 242... 

Transcription factors (such as TFIID for RNA polymerase II) help to initiate transcription. The requirements for termination of transcription in eukaryotes are not well understood. All transcription can be inhibited by actinomycin D. In addition, RNA polymerase II is inhibited by a-amanitin (a toxin from certain mushrooms). These points are summarized in Table 1-3-1,... 

Inhibited by rifampin Actinomycin D RNAP 2 inhibited by a-amanitin (mushrooms) Actinomycin D... 

Amatoxins are a family of cyclic peptides, with oc-amanitin and 3-amanitin (Figure 3.1) accounting for >90% of the total amatoxins. In A. virosa, mushrooms collected in Virginia a-amanitin found to be completely replaced by amaninamide (Figure 3.1). The peptides are not destroyed by cooking and... 

Figure 3.1 Structures of the main amatoxins a-amanitin, (3-amanitin, and amaninamide.

Saviuc, P., Dematteis, M., Mezin, P., Danel, V. and Mallaret, M. (2003). Toxicity of the Clitocybe amoenolens mushroom in rat, Vet. Hum. Toxicol, 45, 180-182. Seeger, R. (1984). Zeitungspapiertest fiir Amanitine - falsch-positive Ergebnisse, Z. 

The statins, lovastatin (L), simvastatin (S), pravastatin (P), fluvastatin (F), cerivastatin, and atorvastatin, inhibit HMG CoA reductase. The active group of L, S, P, and F (or their metabolites) resembles that of the physiological substrate of the enzyme (A). L and S are lactones that are rapidly absorbed by the enteral route, subjected to extensive first-pass extraction in the liver, and there hydrolyzed into active metabolites. P and F represent the active form and, as acids, are actively transported by a specific anion carrier that moves bile acids from blood into liver and also mediates the selective hepatic uptake of the mycotoxin, amanitin (A), Atorvastatin has the longest duration of action. 

Transcription is catalyzed by DNA-dependent RNA polymerases. These act in a similar way to DNA polymerases (see p. 240), except that they incorporate ribonucleotides instead of deoxyribonucleotides into the newly synthesized strand also, they do not require a primer. Eukaryotic cells contain at least three different types of RNA polymerase. RNA polymerase I synthesizes an RNA with a sedimentation coef cient (see p. 200) of 45 S, which serves as precursor for three ribosomal RNAs. The products of RNA polymerase II are hnRNAs, from which mRNAs later develop, as well as precursors for snRNAs. Finally, RNA polymerase III transcribes genes that code for tRNAs, 5S rRNA, and certain snRNAs. These precursors give rise to functional RNA molecules by a process called RNA maturation (see p. 246). Polymerases II and III are inhibited by a-amanitin, a toxin in the Amanita phalloides mushroom. 

DNA-directed RNA polymerase [EC 2.1.1.6] catalyzes the DNA-template-directed extension of the 3 -end of an RNA strand by one nucleotide at a time thus, n nucleoside triphosphate generate RNA and n pyrophosphate. The enzyme can initiate a chain de novo. Three forms of the enzyme have been distinguished in eukaryotes on the basis of sensitivity of a-amanitin and the type of RNA synthesized. See also Replicase... 

DETAILS - The toxicity of certain amanita mush rooms has been well known for centuries. The main toxic species in the United States are Amanita phalloides (Deathcupor Destroying Angel), A. verna, and A. virosa. They contain a mixture of the toxins amanitin, phallpidm, and phalloin. Heat weakens or destroys the toxins, as evidenced by the fact that fresh pressed Amanitajuice is three times more toxic than the boiled juice. There is no antidote for these toxins -treatment is largely symptomatic. The liver is the main target ana is virtually destroyed upon short... 

This mushroom produces the toxin, a-amanitin, a cyclic octapeptide having several modified amino acids and a central purine, which strongly binds to and inhibits RNA pal ii and thereby blocirs elongation. 

RNA pol II is essential for proper function of cells in all tissues and organs, but potentially fatal liver and kidney failure is the main risk for victims of a-amanitin poisoning. 

Due to the relatively high flexibility of cyclic peptides of larger ring size an additional cyclization is sometimes used to constrain their conformation, even by nature, e.g. amanitins and phalloidins. 316 For this purpose primarily side-chain-to-side-chain cyclization is adopted, e.g. Glu/Asp versus Lys or disulfide bridges 1322 alternatively, even the principle of backbone cyclization is applied (see Section 6.8.4)J29>80 323>3241... 

Molecular a-amanitin/ cyclopept./selective inhibits of eukaryotic RNA... 

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