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Publication Date
1981
Description
Crownvetch (Coronilla varia L.) now has limited use in the U.S.A. as a forage crop for ruminant animals. Even though crown vetch forage can contain high amounts of nutrients, intake by ruminants may be reduced. Toxicity problems upon feeding crownvetch to nonmminants have been traced to 3-nitropropanoic acid (NPA), which occurs esterified to glucose in the plant. Understanding mechanisms of toxicity in nonruminants will be helpful in avoiding livstock losses and in treating poisoned animals. Symptoms of NPA toxicity are similar in rats, mice, meadow voles, chickens, and rabbits and probably reflect central nervous system disorders and oxygen deprivation. The other major symptom of NPA poisoning in animals is elevated serum levels of methemoglobin, a nonfunctioning form of hemoglobin, but this condition by itself does not cause death. NP A metabolism in nonruminants evidently produces nitrite ions, which combine with hemoglobin to form methemoglobin. Recent data indicate that NPA might be oxidized by a liver microsomal monooxygenase, thus producing nitrite. However, some additional mechanism is needed to explain NP A toxicity. Investigators have found that approximately 1 % of NPA in the circulation of intoxicated animals is converted to a dianionic carbanion and that the NPA carbanion concentration is sufficiently high to inhibit succinate dehydrogenase irreversibly. Under these conditions, NPA carbanion also competitively inhibits fumarase. These two mitochondrial enzymes catalyze sequential steps in the Krebs cycle, both essential to normal respiration. Two chemical mechanisms for inhibition of succinate dehydrogenase by NP A carbanion have been proposed; the mechanism least acceptable on chemical grounds accounts for nitrite appearance in animals (as methemoglobin), but the second, for which the chemical evidence is most convincing, does not ac• count for nitrite release from NPA. NPA apparently acts in two ways in exerting its toxic effects: (1) inhibition of two mitochondrial enzymes essential to respiration, succinate dehydrogenase (irreversibly) and fumarase (competitively); and (2) methemoglobin formation as a result of metabolic breakdown of NPA to nitrite ion.
Citation
Bustine, D L. and Moyer, B G., "Review of Mechanisms of Toxicity of 3-Nitropropanoic Acid in Nonruminant Animals" (1981). IGC Proceedings (1977-2023). 25.
(URL: https://uknowledge.uky.edu/igc/1981/section11/25)
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Agricultural Science Commons, Agronomy and Crop Sciences Commons, Plant Biology Commons, Plant Pathology Commons, Soil Science Commons, Weed Science Commons
Review of Mechanisms of Toxicity of 3-Nitropropanoic Acid in Nonruminant Animals
Crownvetch (Coronilla varia L.) now has limited use in the U.S.A. as a forage crop for ruminant animals. Even though crown vetch forage can contain high amounts of nutrients, intake by ruminants may be reduced. Toxicity problems upon feeding crownvetch to nonmminants have been traced to 3-nitropropanoic acid (NPA), which occurs esterified to glucose in the plant. Understanding mechanisms of toxicity in nonruminants will be helpful in avoiding livstock losses and in treating poisoned animals. Symptoms of NPA toxicity are similar in rats, mice, meadow voles, chickens, and rabbits and probably reflect central nervous system disorders and oxygen deprivation. The other major symptom of NPA poisoning in animals is elevated serum levels of methemoglobin, a nonfunctioning form of hemoglobin, but this condition by itself does not cause death. NP A metabolism in nonruminants evidently produces nitrite ions, which combine with hemoglobin to form methemoglobin. Recent data indicate that NPA might be oxidized by a liver microsomal monooxygenase, thus producing nitrite. However, some additional mechanism is needed to explain NP A toxicity. Investigators have found that approximately 1 % of NPA in the circulation of intoxicated animals is converted to a dianionic carbanion and that the NPA carbanion concentration is sufficiently high to inhibit succinate dehydrogenase irreversibly. Under these conditions, NPA carbanion also competitively inhibits fumarase. These two mitochondrial enzymes catalyze sequential steps in the Krebs cycle, both essential to normal respiration. Two chemical mechanisms for inhibition of succinate dehydrogenase by NP A carbanion have been proposed; the mechanism least acceptable on chemical grounds accounts for nitrite appearance in animals (as methemoglobin), but the second, for which the chemical evidence is most convincing, does not ac• count for nitrite release from NPA. NPA apparently acts in two ways in exerting its toxic effects: (1) inhibition of two mitochondrial enzymes essential to respiration, succinate dehydrogenase (irreversibly) and fumarase (competitively); and (2) methemoglobin formation as a result of metabolic breakdown of NPA to nitrite ion.
