# 3-Nitropropionic acid
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{{lowercase title}}
{{Chembox
| Name = β-Nitropropionic acid
| ImageFile = 3-Nitropropanoic acid.png
| ImageSize = 200px
| ImageAlt =
| ImageCaption =
| OtherNames = 3-NPA
β-Nitropropionic acid
Hiptagenic acid
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](/source/mycotoxin) which is severely toxic to humans. It is a potent suicidal inhibitor of [succinate dehydrogenase](/source/succinate_dehydrogenase),[{{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}}] an enzyme in the [citric acid cycle](/source/citric_acid_cycle) and [mitochondrial energy chain](/source/Mitochondrion).[{{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}}] Mild cases of exposure give rise to nausea, vomiting, and stomach ache, while severe cases lead to brain damage or death.[{{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}}] There is no known antidote to 3-nitropropionic acid poisoning.[{{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 }}]
3-nitropropionic acid is produced by a number of fungi, most notably in the [''Aspergillus''](/source/Aspergillus_flavus) family, and may be found in food such as in [sugar cane](/source/sugar_cane)[ as well as Japanese fungally fermented staples, including [miso](/source/miso), [soy sauce](/source/soy_sauce), [katsuobushi](/source/katsuobushi),][{{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}}] [coconuts](/source/coconuts)[{{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}}] and some [traditional Chinese medicines](/source/Traditional_Chinese_medicine).[{{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}}] 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.[{{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 }}]{{AI-retrieved source|date=March 2026|checked=no}}[{{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}}]
== Health effects ==
=== Mechanism of action ===
3-nitroprionionic acid has a similar molecular structure to the biological molecule [succinate](/source/succinate), a component of the [tricarboxylic acid cycle](/source/Citric_acid_cycle).[{{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 }}]{{AI-retrieved source|date=March 2026|checked=no}} As such, 3-nitropropionic acid is able to competitively and irreversibly bind to the [flavin](/source/Flavin_group) component of the [succinate dehydrogenase](/source/succinate_dehydrogenase) enzyme.[{{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 }}] Suicidal deactivation by 3-nitropropionic acid permanently disables affected enzymes from catalysing the oxidation of succinate to [fumarate](/source/fumarate).[ This inhibition interrupts the synthesis of the energy biomolecule [adenosine triphosphate](/source/adenosine_triphosphate) (ATP) and triggers energy depletion and [oxidative stress](/source/oxidative_stress) in affected cells.][{{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}}]
3-nitroprionionic also decreases the activity of [Monoamine oxidase](/source/Monoamine_oxidase) (MAO).[{{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}}] The mechanism is that 3-nitroprionionic induces [reactive oxygen species](/source/reactive_oxygen_species) and oxidizes [dopamine](/source/dopamine) generating dopamine-quinones which can reduce the activity of MAO-A.[{{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](/source/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}}]
=== Symptoms ===
Neuronal death can occur, inducing severe neuromuscular disorders and damage to brain matter, spinal tracts, and the nervous system.[{{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}}] Late onset muscle [dystonia](/source/dystonia) and [neurodegeneration](/source/neurodegeneration) of the [caudate putamen](/source/Striatum) have been observed in humans who were exposed to 3-nitropropionic acid.[{{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}}][{{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 }}][{{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 }}] A study on rats further observed dopamine toxicity alongside acute [encephalopathy](/source/encephalopathy) and [dystonia](/source/dystonia).[{{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 }}]
=== Use in medical research ===
Recent studies have found that because 3-nitropropionic acid is a [mitochondrial](/source/Mitochondrial_disease) [toxin](/source/toxin), it can produce [striatal](/source/Striatum) alterations in rats similar to those observed in the [brain](/source/brain) of [Huntington's disease](/source/Huntington's_disease) (HD) patients. As such, 3-nitropropionic acid has been used as an animal model for HD and other such neurodegenerative diseases.[{{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 }}] Administration of the [cannabinoid receptor](/source/cannabinoid_receptor) [agonist](/source/agonist) [WIN55212-2](/source/WIN_55%2C212-2) 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](/source/lipid_peroxidation), by activation of the [CB1](/source/Cannabinoid_receptor_type_1) receptor.[{{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}}]
== 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](/source/mycotoxin), 3-nitropropionic acid is naturally produced by some fungi that infest plants and vegetables.[ These fungi include ''[Aspergillus flavus](/source/Aspergillus_flavus),'' ''[Aspergilllus parasiticus](/source/Aspergillus_parasiticus),'' and of the genus ''[Arthrinium](/source/Arthrinium),'' which grow in soil, decaying vegetation, hay, and grains, and are therefore able to contaminate grains before harvest and in storage.][{{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 }}][{{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}}] 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](/source/Cereal) (corn, sorghum, wheat, rice)
* [Oilseeds](/source/Oilseeds) (soybean, peanut, sunflower and cotton seeds)
* [Spices](/source/Spice) (chili peppers, black pepper, coriander, turmeric and ginger)
* [Tree nuts](/source/Tree_nuts) (pistachio, almond, walnut, coconut and Brazil nuts
[Extreme weather](/source/Extreme_weather), stressed [crop](/source/crop) growth conditions, as well as [storage](/source/Food_storage) conditions (like [moisture](/source/moisture))[{{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}}] 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](/source/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.[{{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}}]
=== 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.