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| Names | |
|---|---|
| Other names Tremortin | |
| Identifiers | |
3D model (JSmol) | |
| ChemSpider |
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| ECHA InfoCard | 100.162.141 |
| UNII | |
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| Properties | |
| C37H44ClNO6 | |
| Molar mass | 633.20136 |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Penitrem A (tremortin) is an indole-diterpenoidmycotoxin produced by certain species ofAspergillus,Claviceps, andPenicillium, which can be found growing on various plant species such asryegrass.[1] Penitrem A is one of manysecondary metabolites following the synthesis ofpaxilline inPenicillium crostosum.[2] Penitrem A poisoning in humans and animals usually occurs through the consumption of contaminated foods by mycotoxin-producing species, which is then distributed through the body by the bloodstream.[2] It bypasses theblood-brain barrier to exert its toxicological effects on thecentral nervous system.[2] In humans, penitrem A poisoning has been associated with severe tremors,hyperthermia,nausea/vomiting,diplopia, andbloody diarrhea.[2] In animals, symptoms of penitrem A poisoning has been associated with symptoms ranging from tremors, seizures, and hyperthermia toataxia andnystagmus.[2]
Roquefortine C has been commonly detected in documented cases of penitrem A poisoning, making it a possiblebiomarker for diagnoses.[3]
Penitrem A impairs GABAergic amino acid neurotransmission and antagonizes high-conductanceCa2+-activated potassium channels in both humans and animals.[4] Impairment of the GABAergic amino acid neurotransmission comes with the spontaneous release of the excitatory amino acidsglutamate andaspartate as well as the inhibitory neurotransmitterγ-aminobutyric acid (GABA).[4] The sudden release of these neurotransmitters results in imbalanced GABAergic signalling, which gives rise to neurological disorders such as the tremors associated with penitrem A poisoning.[4]
Penitrem A also induces the production ofreactive oxygen species (ROS) in theneutrophil granulocytes of humans and animals.[2] Increased ROS production results in tissue damage in the brain and other afflicted organs as well as hemorrhages in acute poisonings.[2]
InPenicillium crustosum, synthesis of penitrem A and othersecondary metabolites follows the synthesis ofpaxilline.[5] Synthesis of penitrem A involves six oxidative-transformation enzymes (fourcytochrome P450 monooxygenases and twoflavin adenine dinucleotide (FAD)-dependentmonooxygenases), twoacetyltransferases, oneoxidoreductase, and oneprenyltransferase.[5] These enzymes are encoded by a cluster of genes used in paxilline synthesis and penitrem A-F synthesis.[5] The pathway is described below:
