Hiptagenic Acid, a Toxic Component of
            <i>Indigofera endecaphylla</i>

Morris, M. P.; Pagan, C; Warmke, H. E.

doi:10.1126/science.119.3088.322

Cited by 69 publications

(19 citation statements)

References 2 publications

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“…This is 20 times greater than the Ki for malonate and about half of the apparent Km value for succinate. It is unlikely that a competitive inhibitor with this degree of affinity would explain the observed toxicity of 3-nitropropionate (7)(8)(9)(10) 3-nitropropionate in purified and soluble preparations of beef heart.suecinate dehydrogenase and stated that 3-nitropropionate "progressively and irreversibly inactivates succinate dehydrogenase in a process which is antagonized by succinate or malonate." Although this statement is qualitatively accordant with the results reported here, the supporting evidence has not been published.…”

Section: Resultsmentioning

confidence: 99%

3-Nitropropionate, the toxic substance of Indigofera , is a suicide inactivator of succinate dehydrogenase

Alston

Mela

Bright

1977

Proc. Natl. Acad. Sci. U.S.A.

363

202

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We have shown that 3-nitropropionate, an isoelectronic analogue of succinate, is a suicide inactivator of succinate dehydrogenase [succinate:(acceptor) However, the precise mechanism of inactivation, as well as mechanistic extrapolations to the oxidation of succinate, must await the elucidation of the structure of the modified enzyme. We can now explain the toxicity of plants such as Indigofera endecaphylla for mammals and fowl as being due to the irreversible blockage of the Krebs cycle by 3-nitropropionate carbanion.Nitroalkanes are good substrates for the flavoenzymes D-amino acid oxidase, glucose oxidase, and L-amino acid oxidase (1-5). The nitroalkane carbanions are many orders of magnitude more reactive than their conjugate carbon acids and, in one case (6), even more reactive than the best physiological substrates (e.g., nitroethane anion compared to glucose with glucose oxidase). Most importantly, and in contrast to any physiological substrate, the chemical mechanism of the enzymic oxidation of nitroalkanes is understood in great detail. For D-amino acid oxidase and nitroethane, it was shown (2) that the substrate carbanion attacks the flavin at N-5 in the rate-determining step to form a covalent adduct (pathway 1 in Eq. 1) from which nitrite is eliminated rapidly to form a highly reactive N-5 iminium adduct. In the normal catalytic cycle (pathway 2 in Eq. 1) the iminium is rapidly hydrated to form an N-5 carbinolamine from which reduced flavin is also rapidly eliminated to form the product acetaldehyde. However, the pivotal N-5 iminium intermediate, as would be expected, is highly reactive with a variety of nucleophiles in addition to H20 (2, 5). Those having unbonded electron pairs (such as NH3, NH20H, and mercap- Second, it occurred to us that, in contrast to D-amino acid oxidase and nitroethane (2)

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Section: Resultsmentioning

confidence: 99%

3-Nitropropionate, the toxic substance of Indigofera , is a suicide inactivator of succinate dehydrogenase

Alston

Mela

Bright

1977

Proc. Natl. Acad. Sci. U.S.A.

363

202

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“…In 1950s, this compound was associated with poisoning episodes in mammals in the United States and China, where consumption of sugarcane contaminated with the fungus Arthrinium occurred (Ludolph et al 1991). The studies investigating intoxication problems in animals contributed to the identification of 3-NPA as the main toxic agent of the plant Indigofera endecaphylla (Morris et al 1954). The toxic effects caused by 3-NPA have still not been fully elucidated, in which is associated with its similarity to the succinate molecule (Fig 1B), acting as a suicide agent by inactivating the enzyme succinate dehydrogenase in mitochondria (Alston et al 1977).…”

Section: Introductionmentioning

confidence: 99%

3-Nitropropionic acid production by the endophytic Diaporthe citri: Molecular taxonomy, chemical characterization, and quantification under pH variation

et al. 2016

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“…In the proposed biosynthetic pathway of pyrrolnitrin, PrnD catalyzes the oxidation of the amino group of aminopyrrolnitrin (Aprn) to a nitro group, forming pyrrolnitrin (22). Arylamine oxygenases seem to be widespread and are used in diverse metabolic reactions (6,11,13,16,17,19). However, PrnD is the only biochemically characterized example of an arylamine N-oxygenase involved in arylnitro group formation.…”

mentioning

confidence: 99%

Probing the Substrate Specificity of Aminopyrrolnitrin Oxygenase (PrnD) by Mutational Analysis

Lee

Ang²,

Zhao³

2006

J Bacteriol

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Molecular modeling and mutational analysis (site-directed mutagenesis and saturation mutagenesis) were used to probe the molecular determinants of the substrate specificity of aminopyrrolnitrin oxygenase (PrnD) from Pseudomonas fluorescens Pf-5. There are 17 putative substrate-contacting residues, and mutations at two of the positions, positions 312 and 277, could modulate the enzyme substrate specificity separately or in combination. Interestingly, several of the mutants obtained exhibited higher catalytic efficiency (approximately two-to sevenfold higher) with the physiological substrate aminopyrrolnitrin than the wild-type enzyme exhibited.

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Hiptagenic Acid, a Toxic Component of Indigofera endecaphylla

Cited by 69 publications

References 2 publications

3-Nitropropionate, the toxic substance of Indigofera , is a suicide inactivator of succinate dehydrogenase

3-Nitropropionate, the toxic substance of Indigofera , is a suicide inactivator of succinate dehydrogenase

3-Nitropropionic acid production by the endophytic Diaporthe citri: Molecular taxonomy, chemical characterization, and quantification under pH variation

Probing the Substrate Specificity of Aminopyrrolnitrin Oxygenase (PrnD) by Mutational Analysis

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