シクロ(L-Ala-D-Thr-L-Cys(1)-L-c4Hyp-L-Ala-L-Trp2(1)-4-ヒドロキシ-L-Leu-)

Phalloin and gamma-amanitin were detected within the 1st day and phalloidin within the 2nd day in the urine of rats after the administration of amanita phalloides extracts. [HSDB] Intraperitoneal LD50 (mouse) = 1 mg/kg; [RTECS] See Phalloidin.

THE HISTORY OF TOXIC COMPONENTS MAY BE DIVIDED INTO 2 PERIODS. THE 1ST STUDIES BEGAN IN THE LATE 18TH CENTURY AND RESULTED IN DISTINGUISHING BETWEEN NON-TOXIC HEMOLYSIN OR PHALLINE, AND A POORLY DEFINED TOXIC COMPOUND. THE 2ND PERIOD BEGAN WITH THE ISOLATION OF PHALLOIDINE IN 1937, FOLLOWED BY ISOLATION OF ALPHA, BETA AND GAMMA AMANITINE AND PHALLOINE. CLASSIFICATION, STRUCTURE, CONCENTRATIONS, TOXICITY IN ANIMALS AND STRUCTURE-ACTIVITY RELATIONSHIPS ARE DISCUSSED FOR THESE. ALSO REVIEWED ARE DATA ON SYNTHESIS OF TOXIN CONSTITUENTS, RESEARCH ON THE ANTITOXIN, ANTAMANIDE.[THEVENIN M ET AL; AMANITA PHALLOIDES AND ITS TOXINS: I. REVIEW OF RESEARCH ON THE IDENTITY OF THE TOXIC COMPONENTS; EUR J TOXICOL ENVIRON HYG 9(4) 197 (1976)]

Phallotoxins bind actin, preventing its depolymerization and poisoning the cell. They bind specifically at the interface between F-actin subunits, locking adjacent subunits together. This leads to a decrease in the rate constant for the dissociation of actin subunits from filament ends, which essentially stabilizes actin filaments through the prevention of filament depolymerization. Moreover, they inhibit the ATP hydrolysis activity of F-actin. (L1183, A2465)

Hypovolemic shock; Gastrointestinal symptoms occur after a latent period and include abdominal pain, vomiting, and watery diarrhea. Neurologic symptoms are related to hepatic failure and may include encephalopathy, somnolence, confusion, coma and seizures (L1160).

THE MOST SERIOUS FORM OF MYCETISMUS IS PRODUCED BY GALERINA SPECIES, AMANITA VERNA, AMANITA VIROSA, AND AMANITA PHALLOIDES, WHICH ARE FAIRLY COMMON IN BOTH NORTH AMERICA AND EUROPE. THESE SPECIES ACCOUNT FOR 90% OF ALL FATAL CASES. THE PRINCIPAL TOXINS ARE THE PHALLOIDINS, A GROUP OF CYCLIC HEPTAPEPTIDES THAT APPEAR TO INHIBIT PROTEIN SYNTHESIS, AND THE AMANITINS, WHICH INHIBIT RNA POLYMERASE II AND HENCE INTERFERE WITH THE SYNTHESIS OF MESSENGER RNA. THE TOXINS DISRUPT HEPATIC CELL MEMBRANES AND THE STRUCTURE OF THE ENDOPLASMIC RETICULUM. /PHALLOIDINS/

THE PHALLOTOXINS ARE SOMETIMES SAID TO BE RESPONSIBLE FOR...INITIAL GASTROENTERITIS /OF MUSHROOM POISONING/... /PHALLOTOXINS/

THE PHALLOTOXINS (WHICH INCLUDE PHALLOIDIN) POSSESS A COMMON CYCLIC HEPTAPEPTIDE SKELETON WITH SOME UNUSUAL AMINO ACIDS. AT LEAST IN THE CASE OF PHALLOIDIN, WHICH MAY OR MAY NOT HAVE TO BE ALTERED CHEMICALLY BY THE LIVER BEFORE IT ACQUIRES ITS CHARACTERISTIC ABILITY TO INJURE THAT ORGAN, CYTOTOXICITY IS ASSOCIATED WITH A THIOETHER LINKAGE BETWEEN CYSTEINE AND TRYPTOPHAN IN THE TOXIN MOLECULE.

Oligopeptide similar to phalloidin. [ChemIDplus]

Prophalloin is one of a group of toxins from the death cap (Amanita phalloides) known as phallotoxins. (L996)

COUPLING OF THE S-CHLORIDE OF BOC TERT-BUTYLOXYCARBONYL-ALANYL-D-THREONYL-CYSTEINYL-ALLO-HYDROXYPROLINE WITH ALANYL-TRYPTOPHYL-GAMMA-HYDROXYLEUCINE LACTONE GAVE A THIOETHER, WHICH ON CYCLIZATION YIELDED BOC-SECOPHALLOIN LACTONE. REMOVAL OF THE BOC RESIDUE, OPENING OF THE LACTONE RING AND A 2ND CYCLIZATION LED TO PHALLOIN, WHICH PROVED IDENTICAL WITH THE NATURAL TOXIN IN PHYSICAL AND TOXICOLOGICAL RESPECTS.