User:VivaVis/sandbox
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| Other names
Aureine
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| Identifiers | |
3D model (JSmol)
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| ChEBI | |
| ChEMBL | |
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| KEGG | |
PubChem CID
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| Properties | |
| C18H25NO5 | |
| Density | 1.25 g/cm3 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Senecionine is an organic compound with the chemical formula C
18H
25NO
5. It is produced by Senecio species and classified as a pyrrolizidine alkaloid. It has a core structure of retronecine which is further esterified by two Isoleucine to form a 12 member lactone ring. The compound is toxic and as alkaloid of the widespread plant Jacobaea vulgaris also problematic for feed stock and human consumption.[1]
Symptoms[edit]
Senacionine poisoning in humans takes on the form of an acute veno-occlusive disease, resulting in numerous detrimental effects, including plural effusions and even cirrhosis of the liver. The physical signs of this veno-occlusive disease primarily consist of upper abdominal discomfort that gradually develops into abdominal swelling. The course of the disease is rapid and often fatal.[2]
In animals, Senacionine and pyrrolizidine alkaloids at large are generally significant due to their poisoning of livestock. Consumption of Senacionine containing plants such as Ragwort, can lead to complications in livestock, even resulting in massive outbreaks. Classic symptoms in animals include liver occlusions but also vascular lesions in the lungs.[3]
Treatments[edit]
To date, no antidote or specific treatment exists for poisoning by pyrrolizidine alkaloids, including senecionine. Patients who undergo renal or hepatic failure as a result of poisoning undergo standard hemodialysis.[4] Given that by the time the pyrrole metabolites reach the liver, it is likely too late to commence any effective procedures, current intervention plans following senecionine poisoning focus on inhibiting metabolism of the alkaloid. An alternative is to add other reactive species such as methionine or cysteine to prevent a pyrrole metabolites from interacting with the hepatocytes of the liver.[5]
Mechanism of Action[edit]
In animals and humans, the primary routes of Senecionine and pyrrolizidine alkaloids after being metabolized are either through hydrolysis of the ester groups or N-oxidation.[6] These routes are generally seen as detoxification mechanisms that promote normal functioning. However, occasional interactions between the alkaloids and mixed function oxidases such as cytochrome P450 lead to dehydrogenation of the pyrrolizidine nucleus to pyrrolic derivatives. These resulting pyrrole metabolites can result in the creation of DNA adducts , primarily in the liver.[7] This cytotoxicity effects the hepatocytes and blood vessels within the liver, leading to the development of tumors or megalocytosis.
Biosynthesis[edit]
In Senecio species, biosynthesis of Senecionine starts from L-Arginine or L-ornithine. Since plants don't have decarboxylase enzyme for L-ornithine, it must be first converted into L-Arginine, which can be readily converted to putrescine. Putrescine gains an aminopropyl group from spermidine in an NAD+ fashion to form homospermidine via homospermidine synthase. The detailed mechanism for this step isn't well understood and it is suspected that imine intermediate is involved. Homospermidine undergo a series of reactions to form the 2 five member rings structure of retronecine. Retronecine is further esterified by two L-isoleucine and modified through a couple of steps to senecionine.
See also[edit]
- Riddelliine, a closely related pyrrolizidine alkaloid
References[edit]
- ^ "Pyrrolizidine Alkaloids—Genotoxicity, Metabolism Enzymes, Metabolic Activation, and Mechanisms". doi:10.1081/DMR-120028426.
{{cite journal}}: Cite journal requires|journal=(help) - ^ "Senecionine". Toxicology Data Network. National Library of Medicine.
- ^ "Senecionine". Toxicology Data Network. National Library of Medicine.
- ^ "Senecionine". Toxicology Data Network. National Library of Medicine.
- ^ "Senecionine". Toxicology Data Network. National Library of Medicine.
- ^ He, Xiaobo; Ma, Liang; Xia, Quingsu; Fu, Peter (2016). "7-N-Acetylcysteine-pyrrole conjugate—A potent DNA reactive metabolite of pyrrolizidine alkaloids". Journal of Food and Drug Analysis. 24 (4): 682–694.
- ^ He, Xiaobo; Ma, Liang; Xia, Quingsu; Fu, Peter (2016). "7-N-Acetylcysteine-pyrrole conjugate—A potent DNA reactive metabolite of pyrrolizidine alkaloids". Journal of Food and Drug Analysis. 24 (4): 682–694.
- Dewick, M,Paul (Feb 4, 2009). Medicinal Natural Products. wiley online. pp. 324–325. doi:10.1002/9780470742761. ISBN 9780470742761.
{{cite book}}: CS1 maint: multiple names: authors list (link)
- ^ "Senecionine". Toxicology Data Network. National Library of Medicine.
- ^ He, Xiaobo; Ma, Liang; Xia, Quingsu; Fu, Peter (2016). "7-N-Acetylcysteine-pyrrole conjugate—A potent DNA reactive metabolite of pyrrolizidine alkaloids". Journal of Food and Drug Analysis. 24 (4): 682–694.