{{lowercase title}}
{{Chembox | Name = β-Nitropropionic acid | ImageFile = 3-Nitropropanoic acid.png | ImageSize = 200px | ImageAlt = | ImageCaption = | OtherNames = 3-NPA<br>β-Nitropropionic acid<br>Hiptagenic acid<br>Bovinocidin | PIN = 3-Nitropropanoic acid | Section1 = {{Chembox Identifiers | CASNo = 504-88-1 | CASNo_Ref = {{cascite|correct|CAS}} | UNII_Ref = {{fdacite|correct|FDA}} | UNII = QY4L0FOX0D | PubChem = 1678 | ChemSpiderID = 1615 | SMILES = C(C[N+](=O)[O-])C(=O)O | StdInChI = 1S/C3H5NO4/c5-3(6)1-2-4(7)8/h1-2H2,(H,5,6) | StdInChIKey = WBLZUCOIBUDNBV-UHFFFAOYSA-N }} | Section2 = {{Chembox Properties | C=3 | H=5 | N=1 | O=4 | MolarMass = | Appearance = | Density = | MeltingPtC = 65-67 | BoilingPt = | Solubility = }} | Section3 = {{Chembox Hazards | MainHazards = | FlashPt = | AutoignitionPt = }} }}
'''3-Nitropropionic acid''' ('''3-NPA''') is a mycotoxin which is severely toxic to humans. It is a potent suicidal inhibitor of succinate dehydrogenase,<ref>{{cite journal |last1=Roberts|first1=Toby John|year=2004|title=3-Nitropropionic Acid Model of Metabolic Stress: Assessment by Magnetic Resonance Imaging|journal=Stroke Genomics|volume=104|pages=203–220|doi=10.1385/1-59259-836-6:203|pmid=15454669}}</ref> an enzyme in the citric acid cycle and mitochondrial energy chain.<ref name=hbs>{{Cite journal |last1=Bendiksen Skogvold|first1=Hanne|last2=Yazdani|first2=Mazyar|last3=Sandås|first3=Elise Mørk|last4=Østeby Vassli|first4=Anja|last5=Kristensen|first5=Erle|last6=Haarr|first6=Dagfinn|last7=Rootwelt|first7=Helge|last8=Elgstøen|first8=Katja Benedikte Prestø|date=2022|title=A pioneer study on human 3-nitropropionic acid intoxication: Contributions from metabolomics|url=https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/jat.4259|journal=Journal of Applied Toxicology|language=en|volume=42|issue=5|pages=818–829|doi=10.1002/jat.4259|pmid=34725838|issn=1099-1263|doi-access=free|hdl=11250/3025093|hdl-access=free}}</ref> Mild cases of exposure give rise to nausea, vomiting, and stomach ache, while severe cases lead to brain damage or death.<ref>{{Cite journal |last=Ming|first=Li|date=1995-01-01|title=Moldy Sugarcane Poisoning— A Case Report with a Brief Review|url=https://www.tandfonline.com/doi/abs/10.3109/15563659509028924|journal=Journal of Toxicology: Clinical Toxicology|volume=33|issue=4|pages=363–367|doi=10.3109/15563659509028924|issn=0731-3810|pmid=7629905|url-access=subscription}}</ref> There is no known antidote to 3-nitropropionic acid poisoning.<ref name=wlcvh>{{Cite journal |last=Van Hooste |first=Wim L. C. |date=2017-02-07 |title=Myoclonic seizure prior to diagnosis of chronic toxic encephalopathy: a case report |journal=Journal of Medical Case Reports |volume=11 |issue=1 |article-number=36 |doi=10.1186/s13256-016-1188-9 |doi-access=free |pmid=28173825 |issn=1752-1947|pmc=5296961 }}</ref>
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<ref name=wlcvh/> as well as Japanese fungally fermented staples, including miso, soy sauce, katsuobushi,<ref>{{cite book |last1=Hocking |first1=Ailsa D. |url=https://books.google.com/books?id=9xlIicZfQ5IC&dq=mycotoxins+katsuobushi&pg=PA7 |title=Advances in Food Mycology |last2=Pitt |first2=John I. |last3=Samson |first3=Robert A. |last4=Thrane |first4=Ulf |date=29 August 2006 |publisher=Springer |isbn=9780387283913}}</ref> coconuts<ref>{{cite journal |last1=Birkelund |first1=T. |last2=Johansen |first2=R. F. |last3=Illum |first3=D. G. |last4=Dyrskog |first4=S. E. |last5=Østergaard |first5=J. A. |last6=Falconer |first6=T. M. |last7=Andersen |first7=C. |last8=Fridholm |first8=H. |last9=Overballe-Petersen |first9=S. |last10=Jensen |first10=J. S. |year=2021 |title=Fatal 3-Nitropropionic Acid Poisoning after Consuming Coconut Water |journal=Emerging Infectious Diseases |volume=27 |issue=1 |pages=278–280 |doi=10.3201/eid2701.202222 |pmc=7774558 |pmid=33350928}}</ref> and some traditional Chinese medicines.<ref>{{cite journal |last1=Wang |first1=X.P. |last2=Yang |first2=R.M. |year=2003 |title=Movement Disorders Possibly Induced by Traditional Chinese Herbs |journal=European Neurology |volume=50 |issue=3 |pages=153–159 |doi=10.1159/000073056 |pmid=14530621 |s2cid=43878555}}</ref> 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.<ref>{{Citation |last1=Hamilton |first1=Bradley F. |chapter=History of 3-Nitropropionic Acid |date=2000 |title=Mitochondrial Inhibitors and Neurodegenerative Disorders |pages=21–33 |editor-last=Sanberg |editor-first=Paul R. |url=https://link.springer.com/chapter/10.1007/978-1-59259-692-8_2?utm_source=chatgpt.com |access-date=2025-04-29 |place=Totowa, NJ |publisher=Humana Press |language=en |doi=10.1007/978-1-59259-692-8_2 |isbn=978-1-59259-692-8 |last2=Gould |first2=Daniel H. |last3=Gustine |first3=David L. |editor2-last=Nishino |editor2-first=Hitoo |editor3-last=Borlongan |editor3-first=Cesario V.|url-access=subscription }}</ref>{{AI-retrieved source|date=March 2026|checked=no}}<ref>{{Cite journal |last1=Liu |first1=X. |last2=Luo |first2=X. |last3=Hu |first3=W. |date=June 1992 |title=Studies on the epidemiology and etiology of moldy sugarcane poisoning in China |journal=Biomedical and Environmental Sciences |volume=5 |issue=2 |pages=161–177 |issn=0895-3988 |pmid=1642790}}</ref>
== 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.<ref>{{Cite journal |last1=Upadhayay |first1=Shubham |last2=Yedke |first2=Narhari Gangaram |last3=Rahi |first3=Vikrant |last4=Singh |first4=Surbhi |last5=Kumar |first5=Sachin |last6=Arora |first6=Anchal |last7=Chandolia |first7=Priyanka |last8=Kaur |first8=Prabhsharan |last9=Kumar |first9=Mandeep |last10=Koshal |first10=Prashant |last11=Jamwal |first11=Sumit |last12=Kumar |first12=Puneet |date=2023-06-01 |title=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 |url=https://link.springer.com/article/10.1007/s11064-023-03868-1?utm_source=chatgpt.com |journal=Neurochemical Research |language=en |volume=48 |issue=6 |pages=1631–1647 |doi=10.1007/s11064-023-03868-1 |pmid=36738367 |issn=1573-6903|url-access=subscription }}</ref>{{AI-retrieved source|date=March 2026|checked=no}} As such, 3-nitropropionic acid is able to competitively and irreversibly bind to the flavin component of the succinate dehydrogenase enzyme.<ref name=taa>{{Cite journal |last1=Alston |first1=T. A. |last2=Mela |first2=L. |last3=Bright |first3=H. J. |date=September 1977 |title=3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=74 |issue=9 |pages=3767–3771 |doi=10.1073/pnas.74.9.3767 |doi-access=free |issn=0027-8424 |pmc=431722 |pmid=269430 |bibcode=1977PNAS...74.3767A }}</ref> Suicidal deactivation by 3-nitropropionic acid permanently disables affected enzymes from catalysing the oxidation of succinate to fumarate.<ref name=taa/> This inhibition interrupts the synthesis of the energy biomolecule adenosine triphosphate (ATP) and triggers energy depletion and oxidative stress in affected cells.<ref name=it>{{Cite journal |last1=Túnez |first1=Isaac |last2=Tasset |first2=Inmaculada |last3=Pérez-De La Cruz |first3=Verónica |last4=Santamaría |first4=Abel |date=2010-02-10 |title=3-Nitropropionic Acid as a Tool to Study the Mechanisms Involved in Huntington's Disease: Past, Present and Future |journal=Molecules |language=en |volume=15 |issue=2 |pages=878–916 |doi=10.3390/molecules15020878 |doi-access=free |issn=1420-3049 |pmc=6263191 |pmid=20335954}}</ref>
3-nitroprionionic also decreases the activity of Monoamine oxidase (MAO).<ref>{{Cite journal |last1=Salman |first1=Mohd |last2=Tabassum |first2=Heen |last3=Parvez |first3=Suhel |date=25 February 2020 |title=Piperine mitigates behavioral impairments and provides neuroprotection against 3-nitropropinoic acid-induced Huntington disease-like symptoms |journal=Nutritional Neuroscience |language=en |volume=25 |issue=1 |pages=100-109 |doi=10.1080/1028415X.2020.1721645 |pmid=32093571}}</ref> The mechanism is that 3-nitroprionionic induces reactive oxygen species and oxidizes dopamine generating dopamine-quinones which can reduce the activity of MAO-A.<ref>{{Cite journal |last1=Herrera-Mundo |first1=Nieves |last2=Sitges |first2=María |date=July 2010 |title=Mechanisms underlying striatal vulnerability to 3-nitropropionic acid |journal=Journal of Neurochemistry |language=en |volume=114 |issue=2 |pages=597-605 |doi=10.1111/j.1471-4159.2010.06789.x |doi-access=free |pmid=20477912}}</ref>
=== Symptoms === Neuronal death can occur, inducing severe neuromuscular disorders and damage to brain matter, spinal tracts, and the nervous system.<ref name=it/><ref>{{Cite journal |last1=Ludolph |first1=A. C. |last2=He |first2=F. |last3=Spencer |first3=P. S. |last4=Hammerstad |first4=J. |last5=Sabri |first5=M. |date=November 1991 |title=3-Nitropropionic Acid - Exogenous Animal Neurotoxin and Possible Human Striatal Toxin |url=https://www.cambridge.org/core/journals/canadian-journal-of-neurological-sciences/article/3nitropropionic-acid-exogenous-animal-neurotoxin-and-possible-human-striatal-toxin/0F665A46A822D5149FDA63A410C448AE |journal=Canadian Journal of Neurological Sciences |language=en |volume=18 |issue=4 |pages=492–498 |doi=10.1017/S0317167100032212 |pmid=1782616 |issn=0317-1671}}</ref> Late onset muscle dystonia and neurodegeneration of the caudate putamen have been observed in humans who were exposed to 3-nitropropionic acid.<ref>{{Cite journal |last1=Gabrielson |first1=K. L. |last2=Hogue |first2=B. A. |last3=Bohr |first3=V. A. |last4=Cardounel |first4=A. J. |last5=Nakajima |first5=W. |last6=Kofler |first6=J. |last7=Zweier |first7=J. L. |last8=Rodriguez |first8=E. R. |last9=Martin |first9=L. J. |last10=de Souza-Pinto |first10=N. C. |last11=Bressler |first11=J. |date=October 2001 |title=Mitochondrial toxin 3-nitropropionic acid induces cardiac and neurotoxicity differentially in mice |journal=The American Journal of Pathology |volume=159 |issue=4 |pages=1507–1520 |doi=10.1016/S0002-9440(10)62536-9 |issn=0002-9440 |pmc=1850498 |pmid=11583977}}</ref><ref>{{Cite journal |last1=Alexi |first1=Tajrena |last2=Hughes |first2=Paul E. |last3=Faull |first3=Richard L. M. |last4=Williams |first4=Chris E. |date=1998-08-03 |title=3-Nitropropionic acid's lethal triplet: cooperative pathways of neurodegeneration |url=https://journals.lww.com/neuroreport/abstract/1998/08030/3_nitropropionic_acid_s_lethal_triplet_.1.aspx |journal=NeuroReport |language=en-US |volume=9 |issue=11 |pages=R57-64 |doi=10.1097/00001756-199808030-00001 |pmid=9721909 |issn=0959-4965|url-access=subscription }}</ref><ref name=cvb>{{Cite journal |last1=Borlongan |first1=Cesario V. |last2=Koutouzis |first2=Theodore K. |last3=Sanberg |first3=Paul R. |date=1997-01-01 |title=3-Nitropropionic acid animal model and Huntington' s disease |url=https://linkinghub.elsevier.com/retrieve/pii/S0149763496000279 |journal=Neuroscience & Biobehavioral Reviews |volume=21 |issue=3 |pages=289–293 |doi=10.1016/S0149-7634(96)00027-9 |pmid=9168265 |issn=0149-7634|url-access=subscription }}</ref> A study on rats further observed dopamine toxicity alongside acute encephalopathy and dystonia.<ref>{{Cite journal |last1=Johnson |first1=John R |last2=Robinson |first2=Bonnie L |last3=Ali |first3=Syed F |last4=Binienda |first4=Zbigniew |date=2000-07-27 |title=Dopamine toxicity following long term exposure to low doses of 3-nitropropionic acid (3-NPA) in rats |url=https://linkinghub.elsevier.com/retrieve/pii/S0378427400002149 |journal=Toxicology Letters |volume=116 |issue=1 |pages=113–118 |doi=10.1016/S0378-4274(00)00214-9 |pmid=10906428 |bibcode=2000ToxL..116..113J |issn=0378-4274|url-access=subscription }}</ref>
=== 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.<ref name=cvb/><ref>{{Cite journal |last1=Miller |first1=Paul J. |last2=Zaborszky |first2=Laszlo |date=1997-07-01 |title=3-Nitropropionic Acid Neurotoxicity: Visualization by Silver Staining and Implications for Use as an Animal Model of Huntington's Disease |url=https://linkinghub.elsevier.com/retrieve/pii/S0014488697965225 |journal=Experimental Neurology |volume=146 |issue=1 |pages=212–229 |doi=10.1006/exnr.1997.6522 |pmid=9225755 |issn=0014-4886|url-access=subscription }}</ref> 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.<ref>{{Cite journal |last1=Maya-López |first1=Marisol |last2=Colín-González |first2=Ana Laura |last3=Aguilera |first3=Gabriela |last4=de Lima |first4=María Eduarda |last5=Colpo-Ceolin |first5=Ana |last6=Rangel-López |first6=Edgar |last7=Villeda-Hernández |first7=Juana |last8=Rembao-Bojórquez |first8=Daniel |last9=Túnez |first9=Isaac |date=2017-02-15 |title=Neuroprotective effect of WIN55,212-2 against 3-nitropropionic acid-induced toxicity in the rat brain: involvement of CB1 and NMDA receptors |journal=American Journal of Translational Research |volume=9 |issue=2 |pages=261–274 |issn=1943-8141 |pmc=5340665 |pmid=28337258}}</ref>
== In nature == thumb|This diagram illustrates the contamination pathway of 3-nitropropionic acid (3-NPA), a mycotoxin produced by ''Aspergillus flavus''. Crops such as sugarcane, coconuts, peanuts, soybeans, rice, and maize serve as host substrates for fungal growth. Once contaminated, these crops can transmit 3-NPA to humans and animals through direct consumption or through derived animal products.
=== Natural occurrence in food crops === As a mycotoxin, 3-nitropropionic acid is naturally produced by some fungi that infest plants and vegetables.<ref name=hbs/> 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.<ref>{{Cite journal |last1=Reddy |first1=K. R. N. |last2=Salleh |first2=B. |last3=Saad |first3=B. |last4=Abbas |first4=H. K. |last5=Abel |first5=C. A. |last6=Shier |first6=W. T. |date=2010-03-01 |title=An overview of mycotoxin contamination in foods and its implications for human health |url=https://www.tandfonline.com/doi/abs/10.3109/15569541003598553 |journal=Toxin Reviews |volume=29 |issue=1 |pages=3–26 |doi=10.3109/15569541003598553 |issn=1556-9543|url-access=subscription }}</ref><ref>{{cite journal |last1=Wei |first1=D. L. |last2=Chang |first2=S. C. |last3=Lin |first3=S. C. |last4=Doong |first4=M. L. |last5=Jong |first5=S. C. |date=1994 |title=Production of 3-nitropropionic acid by Arthrinium species |url=https://agris.fao.org/agris-search/search.do?recordID=US9507900 |journal=Current Microbiology |volume=28 |pages=1–5 |doi=10.1007/BF01575978 |issn=0343-8651 |s2cid=41489212}}</ref> According to the World Health Organization, some of the crops that are commonly affected by ''Aspergillus'' and ''Arthrinium'' fungi include:[https://www.who.int/news-room/fact-sheets/detail/mycotoxins]
* 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)<ref>{{Cite web |last=Jensen |first=Ole |date=Jun 13, 2016 |title=Management of mycotoxin risk in pig production |url=http://www.khl.dk/images/PDF/Svin/2016-06-13_Mykotoksiner.pdf |url-status=dead |archive-url=https://web.archive.org/web/20171010010008/http://www.khl.dk/images/PDF/Svin/2016-06-13_Mykotoksiner.pdf |archive-date=2017-10-10 |access-date=2017-10-09 |website=Powerpoint by Ole Jensen}}</ref> give rise to conditions suitable for 3-nitropropionic acid formation in food crops.
== Notable cases ==
=== Mouldy coconut poisoning in Denmark === 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.<ref>{{Cite journal |last1=Birkelund |first1=Thomas |last2=Johansen |first2=Rakel F. |last3=Illum |first3=Dorte G. |last4=Dyrskog |first4=Stig Eric |last5=Østergaard |first5=Jakob A. |last6=Falconer |first6=Travis M. |last7=Andersen |first7=Chris |last8=Fridholm |first8=Helena |last9=Overballe-Petersen |first9=Søren |last10=Jensen |first10=Jørgen S. |date=January 2021 |title=Fatal 3-Nitropropionic Acid Poisoning after Consuming Coconut Water |journal=Emerging Infectious Diseases |volume=27 |issue=1 |pages=278–280 |doi=10.3201/eid2701.202222 |issn=1080-6059 |pmc=7774558 |pmid=33350928}}</ref>
=== Unexpected 3-NPA identification by LC–MS in Norway === The first reported case of human 3-NPA intoxication in Norway, and the first published human liquid chromatography–mass spectrometry (LC–MS)–based metabolomics study of 3-NPA poisoning worldwide, involved a Norwegian boy with an unknown source of intoxication who was initially suspected of having a mitochondrial disorder. In addition to detecting a large number of altered metabolites, the study identified protective mechanisms that may attenuate the toxic effects of 3-NPA, evidence of increased oxidative stress, and disruption of energy metabolism. The results of the study led to a revision of the toxicological screening panel in Norway, with 3-NPA added to the list of tested compounds.<ref name="hbs" />
== See also ==
* Bongkrek acid, a mycotoxin with similar notable incidents of poisoning via contaminated coconuts
==References== <references responsive="1"></references>
==Further reading==
* {{cite journal |last1=Huang |first1=Li-Shar |last2=Sun |first2=Gang |last3=Cobessi |first3=David |last4=Wang |first4=Andy C. |last5=Shen |first5=John T. |last6=Tung |first6=Eric Y. |last7=Anderson |first7=Vernon E. |last8=Berry |first8=Edward A. |year=2006 |title=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 |url=http://www.jbc.org/content/281/9/5965.full.pdf |journal=Journal of Biological Chemistry |volume=281 |issue=9 |pages=5965–5972 |doi=10.1074/jbc.M511270200 |pmc=1482830 |pmid=16371358 |doi-access=free |bibcode=2006JBiCh.281.5965H }}
{{toxins}}{{DEFAULTSORT:Nitropropionic acid, β-}}
Category:Propionic acids Category:Mycotoxins Category:Nitro compounds Category:Respiratory toxins Category:Monoamine oxidase inhibitors