Penitrem A (tremortin) is an indole-diterpenoid mycotoxin produced by certain species of Aspergillus, Claviceps, and Penicillium, which can be found growing on various plant species such as ryegrass.[1] Penitrem A is one of many secondary metabolites following the synthesis of paxillineinPenicillium 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 the blood-brain barrier to exert its toxicological effects on the central nervous system.[2] In humans, penitrem A poisoning has been associated with severe tremors, hyperthermia, nausea/vomiting, diplopia, and bloody diarrhea.[2] In animals, symptoms of penitrem A poisoning has been associated with symptoms ranging from tremors, seizures, and hyperthermia to ataxia and nystagmus.[2]
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Other names
Tremortin | |
Identifiers | |
3D model (JSmol) |
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ChemSpider |
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ECHA InfoCard | 100.162.141 ![]() |
PubChem CID |
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UNII | |
CompTox Dashboard (EPA) |
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Properties | |
C37H44ClNO6 | |
Molar mass | 633.20136 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Roquefortine C has been commonly detected in documented cases of penitrem A poisoning, making it a possible biomarker for diagnoses.[3]
Penitrem A impairs GABAergic amino acid neurotransmission and antagonizes high-conductance Ca2+-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 acids glutamate and aspartate as well as the inhibitory neurotransmitter γ-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 of reactive oxygen species (ROS) in the neutrophil 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 other secondary metabolites follows the synthesis of paxilline.[5] Synthesis of penitrem A involves six oxidative-transformation enzymes (four cytochrome P450 monooxygenases and two flavin adenine dinucleotide (FAD)-dependent monooxygenases), two acetyltransferases, one oxidoreductase, and one prenyltransferase.[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: