Toxicity and Metabolism of the Conjugates of 3-Nitropropanol and 3-Nitropropionic Acid in Forages Poisonous to Livestock

Abstract

Glycosides of 3-nitro-1-propanol (nitropropanol) and glucose esters of 3-nitro-1-propanoic acid (nitropropionic acid) occur in many forages distributed throughout the world. Systemically, nitropropionic acid irreversibly inactivates succinate dehydrogenase, thereby blocking ATP formation. Nitropropanol is not toxic per se in mammals but is converted to nitropropionic acid by hepatic alcohol dehydrogenase. Nitrotoxins can be metabolized by rumen microbes, which may provide a mechanism for detoxification. At least 20 different ruminal bacteria are known to metabolize the nitrotoxins, but most appear to play a minor role in detoxification. Evidence suggests that an obligate anaerobic nitro-respiring bacterium, Denitrobacterium detoxificans, may be particularly important in conferring protection to animals consuming the nitrotoxins as this bacterium metabolizes the toxins at rates near those by mixed ruminal populations. Rates of ruminal nitrotoxin metabolism can be enhanced by modifying the rumen environment through dietary manipulations, which suggests in vivo enrichment of competent nitrotoxin-metabolizing bacteria such as D. detoxificans.

Detection of 3-nitropropionic acid and cytotoxicity inMucor circinelloides

“…Anderson et al have found that 3-nitropropionic acid is metabolized by the ruminal microbes or rapidly absorbed in the reticulo-rumen (50). When given intravenously, 3-nitropropionic acid was lethal to sheep in a concentration of 52 mg/kg body weight (50). This paper is the first to report on the ability of M. circinelloides for production of 3-nitropropionic acid in culture.…”

“…contaminated sugarcane (53). Anderson et al have found that 3-nitropropionic acid is metabolized by the ruminal microbes or rapidly absorbed in the reticulo-rumen (50). When given intravenously, 3-nitropropionic acid was lethal to sheep in a concentration of 52 mg/kg body weight (50).…”

Proteomic Analysis of Membrane-Associated Proteins from Rat Liver Autophagosomes

“…45; 3x enriched) 199 probably evolved as a protective measure against toxic xenobiotic alcohols, 200 and is capable of metabolizing a variety of alcoholic drugs. 201 Although alcohol oxidation by ADH generates toxic aldehydes, 202 the reaction is actually kinetically favoured in the opposite direction, 203 indicating that ADH may protect against aldehydes generated by bacteria 204 or by microsomal oxidation. 205 With its high affinity for aldehydes, phagophore-associated ADH could possibly be able to recognize aldehyde-protein adducts, ubiquitously formed, e.g., in alcoholic liver disease.…”

Transgenic Leucaena leucocephala expressing the Rhizobium gene pydA encoding a meta-cleavage dioxygenase shows reduced mimosine content

“…Anti-nutritive toxic compounds such as beta-N-oxalyl-L-alpha and beta-diaminopropionic acid are present in Lathyrus sativus seeds [16]. Similarly, 3-nitro-1-propionic acid and 3-nitro-1-propanol are present in the seeds and foliage of many legumes [17]. This work will lead the way for neutralization of toxins in other legumes using similar approaches.…”