Amatoxin

In Amatoxinen are cyclic oligopeptides, which are composed of eight amino acids ( octapeptides ). There are eight amatoxins, of which the α - amanitin, the β - and γ - amanitin amanitin are the best known. Amatoxins come alongside the Phallotoxinen in some species of the genus Amanita (Amanita ) before, eg in the European representatives of Green amanita (A. phalloides ), Kegelhütiger amanita (A. virosa ) and spring Amanita mushroom ( A. verna).

Representative

• Dihyile = (3R, 4R ) -4,5- Dihydroxyisoleucin
• Hyile = (3R, 4S) -4-hydroxyisoleucine
• Hytrp = 6 -hydroxytryptophan

Properties

The amatoxins are resistant to cooking and drying and are not broken down by proteases in the gastrointestinal tract. The reason for this is the ring closure and the bridging of the peptide.

Amanitinen in the first (4R ) -4,5 -dihydroxy -L-isoleucine was discovered as a new amino acid. Furthermore, the L-amino acids aspartic acid, aspartic acid, cysteine, hydroxyproline, isoleucine, glycine and tryptophan, and are included as blocks.

α - amanitin has the empirical formula C39H54N10O14S, a molar mass of 918.84 g / mol CAS number 23109-05-9.

β - amanitin has the empirical formula C39H53N9O15S, a molar mass of 920.0 g / mol and the CAS number 21150-22-1.

γ - amanitin has the empirical formula C39H54N10O12S, a molar mass of 886.98 g / mol CAS number 13567-11-8.

All three are crystalline, colorless, heat- stable and soluble in ethanol, methanol and water.

Biosynthesis

Small peptides as Amanitin are generally constructed of non-ribosomal peptide synthetases. Therefore, it was assumed that even amanitins of NRSPs is synthesized. After the genome has been completely sequenced by A.bisporigera, but found no coding genes NRSP, which excluded this possibility. However, a search for a gene encoding the eight amino acids contained in amanitin IWGIGCNP sequence yielded a gene that was called AMA1. AMA1 of the encoded protein, however, is much longer than the finished amanitin, making post-translational modifications necessary. Further investigation revealed that the amino acid sequence IWGIGCNP is cut out in a first step of Prolyloligopeptidasen from the propeptide. Further processing - which includes inter alia a peptide, and cyclization of the hydroxylation of individual amino acids - is not known yet.

Toxicity

Amatoxins inhibit transcription by blocking of the RNA polymerase. The polymerases of the fungus itself are not affected, in contrast to those of the animals. By inhibition of the mRNA synthesis is not genetically more pass from the nucleus to the cytoplasm, and the protein is blocked.

The different RNA polymerases differ sensitive: Most affected is the polymerase II of eukaryotes, which is responsible for mRNA synthesis. Polymerase I, which is responsible for the synthesis of rRNA, is not, and the polymerase III, which produce tRNA, only weakly inhibited. Due to the diverse functions of proteins, many sites in the organism are affected:

• Enzymes are no longer formed, which they catalyze metabolic processes come to a halt.
• Structural proteins are no longer replaced with aging.
• Hormones ( both peptide and hormones enzymatically formed ) no longer contribute to the control of metabolic processes.
• Membrane receptors such as nerve cells, are not reproduced.

The effects are seen first as diarrhea, which is caused by damage to the epithelial cells of the intestine. Death occurs due to liver failure. The toxicity of amanitins is amplified by the enterohepatic circulation. Through this cycle circulates the Amanitin between liver, gall bladder and intestines and thus remains in the body longer.

Antidote

An antidote is silibinin.

History

α - amanitin was established in 1941, later discovered the other amatoxins of Heinrich Otto Wieland.