 | |
| Names | |
|---|---|
| Preferred IUPAC name
3-Nitropropanoic acid | |
| Other names
3-NPA
β-Nitropropionic acid Hiptagenic acid Bovinocidin | |
| Identifiers | |
3D model (JSmol)
|
|
| ChemSpider | |
| ECHA InfoCard | 100.007.276 |
PubChem CID
|
|
| UNII | |
CompTox Dashboard (EPA)
|
|
| |
| |
| Properties | |
| C3H5NO4 | |
| Molar mass | 119.076 g·mol−1 |
| Melting point | 65–67 °C (149–153 °F; 338–340 K) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
| |
3-Nitropropionic acid (3-NPA) is a mycotoxin which is severely toxic to humans. It is a potent suicidal inhibitor of succinate dehydrogenase,[1] an enyzme in the citric acid cycle and mitochondrial energy chain.[2] Mild cases of exposure give rise to nausea, vomiting, and stomach ache, while severe cases lead to brain damage or death.[3] There is no known antidote to 3-nitropropionic acid poisoning.[4]
3-nitropropionic acid is produced by a number of fungi, most notably in the Aspergillus family, and may be found in food such as in sugar cane[4] as well as Japanese fungally fermented staples, including miso, soy sauce, katsuobushi,[5] coconuts[6] and some traditional Chinese medicines.[7] Several outbreaks of 3-nitropropionic acid poisoning have been linked to contamination of shared food crops, particularly in China, where sugar cane is commonly consumed by children.[8][9]
Health effects
Mechanism of action
3-nitroprionionic acid has a similar molecular structure to the biological molecule succinate, a component of the tricarboxylic acid cycle.[10] As such, 3-nitropropionic acid is able to competitively and irreversibly bind to the flavin component of the succinate dehydrogenase enzyme.[11] Suicidal deactivation by 3-nitropropionic acid permanently disables affected enzymes from catalysing the oxidation of succinate to fumarate.[11] This inhibition interrupts the synthesis of the energy biomolecule adenosine triphosphate (ATP) and triggers energy depletion and oxidative stress in affected cells.[12]
Symptoms
Neuronal death can occur, inducing severe neuromuscular disorders and damage to brain matter, spinal tracts, and the nervous system.[12][13] Late onset muscle dystonia and neurodegeneration of the caudate putamen have been observed in humans who were exposed to 3-nitropropionic acid.[14][15][16] A study on rats further observed dopamine toxicity alongside acute encephalopathy and dystonia.[17]
Use in medical research
Recent studies have found that because 3-nitropropionic acid is a mitochondrial toxin, it can produce striatal alterations in rats similar to those observed in the brain of Huntington's disease (HD) patients. As such, 3-nitropropionic acid has been used as an animal model for HD and other such neurodegenerative diseases.[16][18] Administration of the cannabinoid receptor agonist WIN55212-2 to rats for six consecutive days, before acid dosage, exerted preventive effects on all alterations elicited by the toxin, like mitochondrial dysfunction and lipid peroxidation, by activation of the CB1 receptor.[19]
In nature
Natural occurrence in food cops
As a mycotoxin, 3-nitropropionic acid is naturally produced by some fungi that infest plants and vegetables.[2] These fungi include Aspergillus flavus, Aspergilllus parasiticus, and of the genus Arthrinium, which grow in soil, decaying vegetation, hay, and grains, and are therefore able to contaminate grains before harvest and in storage.[20][21] According to the World Health Organization, some of the crops that are commonly affected by Aspergillus and Arthrinium fungi include:[1]
- Cereals (corn, sorghum, wheat, rice)
- Oilseeds (soybean, peanut, sunflower and cotton seeds)
- Spices (chili peppers, black pepper, coriander, turmeric and ginger)
- Tree nuts (pistachio, almond, walnut, coconut and Brazil nuts
Extreme weather, stressed crop growth conditions, as well as storage conditions (like moisture)[22] give rise to conditions suitable for 3-nitropropionic acid formation in food crops.
Notable cases
Mouldy coconut poisoning
Fatal 3-NPA poisoning as a result of drinking coconut water has been reported in a case where a pre-prepared coconut had been stored at room temperature for a month, instead of being refrigerated.[23]
See also
- Bongkrek acid, a mycotoxin with similar notable incidents of poisoning via contaminated coconuts
References
- ^ Roberts, Toby John (2004). "3-Nitropropionic Acid Model of Metabolic Stress: Assessment by Magnetic Resonance Imaging". Stroke Genomics. 104: 203–220. doi:10.1385/1-59259-836-6:203. PMID 15454669.
- ^ a b Bendiksen Skogvold, Hanne; Yazdani, Mazyar; Sandås, Elise Mørk; Østeby Vassli, Anja; Kristensen, Erle; Haarr, Dagfinn; Rootwelt, Helge; Elgstøen, Katja Benedikte Prestø (2022). "A pioneer study on human 3-nitropropionic acid intoxication: Contributions from metabolomics". Journal of Applied Toxicology. 42 (5): 818–829. doi:10.1002/jat.4259. ISSN 1099-1263. PMID 34725838.
- ^ Ming, Li (1995-01-01). "Moldy Sugarcane Poisoning— A Case Report with a Brief Review". Journal of Toxicology: Clinical Toxicology. 33 (4): 363–367. doi:10.3109/15563659509028924. ISSN 0731-3810. PMID 7629905.
- ^ a b Van Hooste, Wim L. C. (2017-02-07). "Myoclonic seizure prior to diagnosis of chronic toxic encephalopathy: a case report". Journal of Medical Case Reports. 11 (1) 36. doi:10.1186/s13256-016-1188-9. ISSN 1752-1947. PMC 5296961. PMID 28173825.
- ^ Hocking, Ailsa D.; Pitt, John I.; Samson, Robert A.; Thrane, Ulf (29 August 2006). Advances in Food Mycology. Springer. ISBN 9780387283913.
- ^ Birkelund, T.; Johansen, R. F.; Illum, D. G.; Dyrskog, S. E.; Østergaard, J. A.; Falconer, T. M.; Andersen, C.; Fridholm, H.; Overballe-Petersen, S.; Jensen, J. S. (2021). "Fatal 3-Nitropropionic Acid Poisoning after Consuming Coconut Water". Emerging Infectious Diseases. 27 (1): 278–280. doi:10.3201/eid2701.202222. PMC 7774558. PMID 33350928.
- ^ Wang, X.P.; Yang, R.M. (2003). "Movement Disorders Possibly Induced by Traditional Chinese Herbs". European Neurology. 50 (3): 153–159. doi:10.1159/000073056. PMID 14530621. S2CID 43878555.
- ^ Hamilton, Bradley F.; Gould, Daniel H.; Gustine, David L. (2000), "History of 3-Nitropropionic Acid", in Sanberg, Paul R.; Nishino, Hitoo; Borlongan, Cesario V. (eds.), Mitochondrial Inhibitors and Neurodegenerative Disorders, Totowa, NJ: Humana Press, pp. 21–33, doi:10.1007/978-1-59259-692-8_2, ISBN 978-1-59259-692-8, retrieved 2025-04-29
- ^ Liu, X.; Luo, X.; Hu, W. (June 1992). "Studies on the epidemiology and etiology of moldy sugarcane poisoning in China". Biomedical and Environmental Sciences. 5 (2): 161–177. ISSN 0895-3988. PMID 1642790.
- ^ Upadhayay, Shubham; Yedke, Narhari Gangaram; Rahi, Vikrant; Singh, Surbhi; Kumar, Sachin; Arora, Anchal; Chandolia, Priyanka; Kaur, Prabhsharan; Kumar, Mandeep; Koshal, Prashant; Jamwal, Sumit; Kumar, Puneet (2023-06-01). "An Overview of the Pathophysiological Mechanisms of 3-Nitropropionic Acid (3-NPA) as a Neurotoxin in a Huntington's Disease Model and Its Relevance to Drug Discovery and Development". Neurochemical Research. 48 (6): 1631–1647. doi:10.1007/s11064-023-03868-1. ISSN 1573-6903. PMID 36738367.
- ^ a b Alston, T. A.; Mela, L.; Bright, H. J. (September 1977). "3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase". Proceedings of the National Academy of Sciences of the United States of America. 74 (9): 3767–3771. Bibcode:1977PNAS...74.3767A. doi:10.1073/pnas.74.9.3767. ISSN 0027-8424. PMC 431722. PMID 269430.
- ^ a b Túnez, Isaac; Tasset, Inmaculada; Pérez-De La Cruz, Verónica; Santamaría, Abel (2010-02-10). "3-Nitropropionic Acid as a Tool to Study the Mechanisms Involved in Huntington's Disease: Past, Present and Future". Molecules. 15 (2): 878–916. doi:10.3390/molecules15020878. ISSN 1420-3049. PMC 6263191. PMID 20335954.
- ^ Ludolph, A. C.; He, F.; Spencer, P. S.; Hammerstad, J.; Sabri, M. (November 1991). "3-Nitropropionic Acid - Exogenous Animal Neurotoxin and Possible Human Striatal Toxin". Canadian Journal of Neurological Sciences. 18 (4): 492–498. doi:10.1017/S0317167100032212. ISSN 0317-1671. PMID 1782616.
- ^ Gabrielson, K. L.; Hogue, B. A.; Bohr, V. A.; Cardounel, A. J.; Nakajima, W.; Kofler, J.; Zweier, J. L.; Rodriguez, E. R.; Martin, L. J.; de Souza-Pinto, N. C.; Bressler, J. (October 2001). "Mitochondrial toxin 3-nitropropionic acid induces cardiac and neurotoxicity differentially in mice". The American Journal of Pathology. 159 (4): 1507–1520. doi:10.1016/S0002-9440(10)62536-9. ISSN 0002-9440. PMC 1850498. PMID 11583977.
- ^ Alexi, Tajrena; Hughes, Paul E.; Faull, Richard L. M.; Williams, Chris E. (1998-08-03). "3-Nitropropionic acid's lethal triplet: cooperative pathways of neurodegeneration". NeuroReport. 9 (11): R57-64. doi:10.1097/00001756-199808030-00001. ISSN 0959-4965. PMID 9721909.
- ^ a b Borlongan, Cesario V.; Koutouzis, Theodore K.; Sanberg, Paul R. (1997-01-01). "3-Nitropropionic acid animal model and Huntington' s disease". Neuroscience & Biobehavioral Reviews. 21 (3): 289–293. doi:10.1016/S0149-7634(96)00027-9. ISSN 0149-7634. PMID 9168265.
- ^ Johnson, John R; Robinson, Bonnie L; Ali, Syed F; Binienda, Zbigniew (2000-07-27). "Dopamine toxicity following long term exposure to low doses of 3-nitropropionic acid (3-NPA) in rats". Toxicology Letters. 116 (1): 113–118. Bibcode:2000ToxL..116..113J. doi:10.1016/S0378-4274(00)00214-9. ISSN 0378-4274. PMID 10906428.
- ^ Miller, Paul J.; Zaborszky, Laszlo (1997-07-01). "3-Nitropropionic Acid Neurotoxicity: Visualization by Silver Staining and Implications for Use as an Animal Model of Huntington's Disease". Experimental Neurology. 146 (1): 212–229. doi:10.1006/exnr.1997.6522. ISSN 0014-4886. PMID 9225755.
- ^ Maya-López, Marisol; Colín-González, Ana Laura; Aguilera, Gabriela; de Lima, María Eduarda; Colpo-Ceolin, Ana; Rangel-López, Edgar; Villeda-Hernández, Juana; Rembao-Bojórquez, Daniel; Túnez, Isaac (2017-02-15). "Neuroprotective effect of WIN55,212-2 against 3-nitropropionic acid-induced toxicity in the rat brain: involvement of CB1 and NMDA receptors". American Journal of Translational Research. 9 (2): 261–274. ISSN 1943-8141. PMC 5340665. PMID 28337258.
- ^ Reddy, K. R. N.; Salleh, B.; Saad, B.; Abbas, H. K.; Abel, C. A.; Shier, W. T. (2010-03-01). "An overview of mycotoxin contamination in foods and its implications for human health". Toxin Reviews. 29 (1): 3–26. doi:10.3109/15569541003598553. ISSN 1556-9543.
- ^ Wei, D. L.; Chang, S. C.; Lin, S. C.; Doong, M. L.; Jong, S. C. (1994). "Production of 3-nitropropionic acid by Arthrinium species". Current Microbiology. 28: 1–5. doi:10.1007/BF01575978. ISSN 0343-8651. S2CID 41489212.
- ^ Jensen, Ole (Jun 13, 2016). "Management of mycotoxin risk in pig production" (PDF). Powerpoint by Ole Jensen. Archived from the original (PDF) on 2017-10-10. Retrieved 2017-10-09.
- ^ Birkelund, Thomas; Johansen, Rakel F.; Illum, Dorte G.; Dyrskog, Stig Eric; Østergaard, Jakob A.; Falconer, Travis M.; Andersen, Chris; Fridholm, Helena; Overballe-Petersen, Søren; Jensen, Jørgen S. (January 2021). "Fatal 3-Nitropropionic Acid Poisoning after Consuming Coconut Water". Emerging Infectious Diseases. 27 (1): 278–280. doi:10.3201/eid2701.202222. ISSN 1080-6059. PMC 7774558. PMID 33350928.
Further reading
- Huang, Li-Shar; Sun, Gang; Cobessi, David; Wang, Andy C.; Shen, John T.; Tung, Eric Y.; Anderson, Vernon E.; Berry, Edward A. (2006). "3-Nitropropionic Acid is a Suicide Inhibitor of Mitochondrial Respiration That, upon Oxidation by Complex II, Forms a Covalent Adduct with a Catalytic Base Arginine in the Active Site of the Enzyme" (PDF). Journal of Biological Chemistry. 281 (9): 5965–5972. Bibcode:2006JBiCh.281.5965H. doi:10.1074/jbc.M511270200. PMC 1482830. PMID 16371358.
