Biosynthesis of 3-nitropropionic acid in creeping indigo (Indigofera spicata)

Candlish, Elizabeth; Croix, L. J. La; Unrau, A. M.

doi:10.1021/bi00829a026

Cited by 24 publications

(27 citation statements)

References 21 publications

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“…In contrast, no incorporation of the radioactive tracer in 3‐NPA is detected when the D‐isomer is used . The ammonium ion, rather than nitrate, is used for the synthesis of the nitro group of 3‐NPA, with a preference for the amino group of aspartate compared to free ammonium ion . Thus, it was concluded that aspartate must be a direct precursor for the biosynthesis of 3‐NPA in this organism, with a six‐electron oxidation of an amino group to a nitro group and the loss of CO 2 from the α‐carbon atom of aspartate.…”

Section: Biosynthesis Of 3‐npamentioning

confidence: 95%

“…These studies demonstrated the most efficient incorporation of 14 C when the fungus is fed l ‐[4‐ 14 C]‐aspartate . In contrast, no incorporation of the radioactive tracer in 3‐NPA is detected when the D‐isomer is used . The ammonium ion, rather than nitrate, is used for the synthesis of the nitro group of 3‐NPA, with a preference for the amino group of aspartate compared to free ammonium ion .…”

Section: Biosynthesis Of 3‐npamentioning

confidence: 99%

“…The pathway for the biosynthesis of 3‐NPA in plants has been studied in Indigofera spicata with 14 C‐labeled precursors, organic acid fractionation and column chromatography to isolate 3‐NPA and other carbon acids. In addition, gas–liquid chromatographic analysis was used to quantify major organic acids . The study revealed that labeled 3‐NPA is obtained by feeding the plant with [2‐ 14 C]‐malonate or [2‐ 14 C]‐malonyl monohydroxamate .…”

Section: Biosynthesis Of 3‐npamentioning

confidence: 99%

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The biochemistry of the metabolic poison propionate 3‐nitronate and its conjugate acid, 3‐nitropropionate

et al. 2013

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3-Nitropropionate (3-NPA) is a nitro aliphatic compound found in numerous plants and fungi. The nitro compound exists in equilibrium with its conjugate base, propionate 3-nitronate (P3N) and has a pK a approaching the physiological range of 9.1. Since 1920, more than 30 species of plant and fungi have been identified as producing 3-NPA as a means of defense from herbivores. Glycoside products containing moieties of 3-NPA found in parts of the plants most accessible to herbivores can be easily hydrolyzed to free 3-NPA by bacterial enzymes in the gut of animals. In addition to providing a defense mechanism, the nitro compound is an intermediate in the nitrification process of leguminous plants. The synthesis of 3-NPA in these plants and fungi is poorly understood. P3N, which readily forms from 3-NPA at physiological pH, is a potent inhibitor of the key enzyme succinate dehydrogenase in the Krebs cycle and electron transport chain. Inhibition of succinate dehydrogenase in humans and livestock causes neurotoxicity and in some cases death. Several enzymes catalyze the oxidation of 3-NPA or P3N; all contain a noncovalently bound flavin cofactor and are found in the organisms that produce 3-NPA. With, nitronate monooxygenases can quickly and efficiently oxidize P3N to malonic semialdehyde as a means of protecting the organism from killing itself. Although it was discovered almost a century ago, the biochemistry and physiological role of 3-NPA/P3N are just emerging. V C 2013 IUBMB Life, 65(9): [759][760][761][762][763][764][765][766][767][768] 2013

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Section: Biosynthesis Of 3‐npamentioning

confidence: 95%

Section: Biosynthesis Of 3‐npamentioning

confidence: 99%

Section: Biosynthesis Of 3‐npamentioning

confidence: 99%

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The biochemistry of the metabolic poison propionate 3‐nitronate and its conjugate acid, 3‐nitropropionate

et al. 2013

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“…Limited investigations into the plant-based pathways suggest malonic acid as a precursor. 355 Alternatively, investigations into fungal 3-nitropropanoic acid biosynthesis have convincingly demonstrated that this metabolite is derived from L-aspartic acid. 356–362 A series of detailed feeding studies with labeled precursors have mapped every carbon, oxygen, and nitrogen atom of 3-nitropropanoic acid to L-aspartic acid and molecular oxygen and strongly suggest that nitrosuccinate ( 131 ) is a late-stage biosynthetic intermediate (Scheme 27).…”

Section: N–o Bond Forming Enzymesmentioning

confidence: 99%

Heteroatom–Heteroatom Bond Formation in Natural Product Biosynthesis

et al. 2017

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Natural products that contain functional groups with heteroatom-heteroatom linkages (X–X, where X = N, O, S, and P) are a small yet intriguing group of metabolites. The reactivity and diversity of these structural motifs has captured the interest of synthetic and biological chemists alike. Functional groups containing X–X bonds are found in all major classes of natural products and often impart significant biological activity. This review presents our current understanding of the biosynthetic logic and enzymatic chemistry involved in the construction of X–X bond containing functional groups within natural products. Elucidating and characterizing biosynthetic pathways that generate X–X bonds could both provide tools for biocatalysis and synthetic biology, as well as guide efforts to uncover new natural products containing these structural features.

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“…Additionally, in support of both energetic defects and mitochondrial dysfunction as contributors to HD, animal models using mitochondrial neurotoxins have convincingly shown that electron transport chain inhibition can lead to similar behavioral and neuropathological phenotypes associated with HD (Alston et al 1977; Bogdanov et al 1998a; Beal et al 1993; Brouillet et al 1993, 1995; Henshaw et al 1994;Schulz and Beal 1995; Palfi et al 1996). Administration of a naturally occurring plant toxin, 3-nitroproprionic acid (3-NP), an irreversible, and/or malonate, a reversible inhibitor, of succinate dehydrogenase (complex II) of the electron transport chain have both been shown to produce HD-like symptoms (Candlish et al 1969; Ludolph et al 1991; Fig. 5).…”

Section: Huntington’s Diseasementioning

confidence: 99%

Creatine and Its Potential Therapeutic Value for Targeting Cellular Energy Impairment in Neurodegenerative Diseases

2008

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Substantial evidence indicates bioenergetic dysfunction and mitochondrial impairment contribute either directly and/or indirectly to the pathogenesis of numerous neurodegenerative disorders. Treatment paradigms aimed at ameliorating this cellular energy deficit and/or improving mitochondrial function in these neurodegenerative disorders may prove to be useful as a therapeutic intervention. Creatine is a molecule that is produced both endogenously, and acquired exogenously through diet, and is an extremely important molecule that participates in buffering intracellular energy stores. Once creatine is transported into cells, creatine kinase catalyzes the reversible transphosphorylation of creatine via ATP to enhance the phosphocreatine energy pool. Creatine kinase enzymes are located at strategic intracellular sites to couple areas of high energy expenditure to the efficient regeneration of ATP. Thus, the creatinekinase/phosphocreatine system plays an integral role in energy buffering and overall cellular bioenergetics. Originally, exogenous creatine supplementation was widely used only as an ergogenic aid to increase the phosphocreatine pool within muscle to bolster athletic performance. However, the potential therapeutic value of creatine supplementation has recently been investigated with respect to various neurodegenerative disorders that have been associated with bioenergetic deficits as playing a role in disease etiology and/or progression which include; Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), and Huntington's disease. This review discusses the contribution of mitochondria and bioenergetics to the progression of these neurodegenerative diseases and investigates the potential neuroprotective value of creatine supplementation in each of these neurological diseases. In summary, current literature suggests that exogenous creatine supplementation is most efficacious as a treatment paradigm in Huntington's and Parkinson's disease but appears to be less effective for ALS and Alzheimer's disease.

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Biosynthesis of 3-nitropropionic acid in creeping indigo (Indigofera spicata)

Cited by 24 publications

References 21 publications

The biochemistry of the metabolic poison propionate 3‐nitronate and its conjugate acid, 3‐nitropropionate

The biochemistry of the metabolic poison propionate 3‐nitronate and its conjugate acid, 3‐nitropropionate

Heteroatom–Heteroatom Bond Formation in Natural Product Biosynthesis

Creatine and Its Potential Therapeutic Value for Targeting Cellular Energy Impairment in Neurodegenerative Diseases

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