Penitrem A
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| Names | |
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| Other names
Tremortin
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| Identifiers | |
3D model (
JSmol ) |
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| ChemSpider | |
ECHA InfoCard
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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).
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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 paxilline in Penicillium 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]
Roquefortine C has been commonly detected in documented cases of penitrem A poisoning, making it a possible biomarker for diagnoses.[3]
Mechanism of action
Penitrem A impairs GABAergic amino acid neurotransmission and antagonizes high-conductance
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]
Synthesis
In
- Oxidoreductase catalyzes the reduction of paxilline's ketone and also adds a dimethylallyl group to its aromatic ring.[5]
- Acetyltransferases catalyze the removal of the intermediate's lower right-hand hydroxyl group and reduce of one of the nearby methyl groups to a methylene group.[5]
- Oxidative-transformation enzyme catalyzes the addition of a hydroxyl group to the intermediate's dimethylallyl group. The dimethylallyl's double bond migrates down one carbon.[5]
- Prenyltransferase catalyzes the formation of a dimethyl-cyclopentane and a cyclobutane using the intermediate's aromatic ring-alcohol group.[5]
- Oxidative-transformation enzyme catalyzes the formation of a methylenecyclohexane using the intermediate's dimethyl-cyclopentane, forming secopenitrem D.[5]
- Oxidative-transformation enzyme catalyzes the formation of a cyclooctane using cyclobutane's alcohol group and the carbon joining secopenitrem D's cyclohexane and cyclopentane, forming penitrem D.[5]
- Oxidative-transformation enzyme catalyzes the addition a chlorine atom at penitrem D's aromatic ring, forming penitrem C.[5]
- Oxidative-transformation enzyme catalyzes the formation of an oxane-double bond, forming penitrem F.[5]
- Oxidative-transformation enzyme catalyzes the addition of a hydroxyl group at the carbon joining penitrem F's methylenecyclohexane and cyclobutane, forming penitrem A.[5]