3-Nitropropionic acid
3-Nitropropionic acid is a mycotoxin which is severely toxic to humans. It is a potent suicidal inhibitor of succinate dehydrogenase, an enyzme in the citric acid cycle and mitochondrial energy chain. Mild cases of exposure give rise to nausea, vomiting, and stomach ache, while severe cases lead to brain damage or death. There is no known antidote to 3-nitropropionic acid poisoning.
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 as well as Japanese fungally fermented staples, including miso, soy sauce, katsuobushi, coconuts and some traditional Chinese medicines. 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.
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. As such, 3-nitropropionic acid is able to competitively and irreversibly bind to the flavin component of the succinate dehydrogenase enzyme. Suicidal deactivation by 3-nitropropionic acid permanently disables affected enzymes from catalysing the oxidation of succinate to fumarate. This inhibition interrupts the synthesis of the energy biomolecule adenosine triphosphate and triggers energy depletion and oxidative stress in affected cells.Symptoms
Neuronal death can occur, inducing severe neuromuscular disorders and damage to brain matter, spinal tracts, and the nervous system. Late onset muscle dystonia and neurodegeneration of the caudate putamen have been observed in humans who were exposed to 3-nitropropionic acid. A study on rats further observed dopamine toxicity alongside acute encephalopathy and dystonia.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 patients. As such, 3-nitropropionic acid has been used as an animal model for HD and other such neurodegenerative diseases. 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.In nature
Natural occurrence in food cops
As a mycotoxin, 3-nitropropionic acid is naturally produced by some fungi that infest plants and vegetables. 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. According to the World Health Organization, some of the crops that are commonly affected by Aspergillus and Arthrinium'' fungi include:- Cereals
- Oilseeds
- Spices
- Tree nuts give rise to conditions suitable for 3-nitropropionic acid formation in food crops.
Notable cases