New Research In
Physical Sciences
Social Sciences
Featured Portals
Articles by Topic
Biological Sciences
Featured Portals
Articles by Topic
- Agricultural Sciences
- Anthropology
- Applied Biological Sciences
- Biochemistry
- Biophysics and Computational Biology
- Cell Biology
- Developmental Biology
- Ecology
- Environmental Sciences
- Evolution
- Genetics
- Immunology and Inflammation
- Medical Sciences
- Microbiology
- Neuroscience
- Pharmacology
- Physiology
- Plant Biology
- Population Biology
- Psychological and Cognitive Sciences
- Sustainability Science
- Systems Biology
3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase

Abstract
We have shown that 3-nitropropionate, an isoelectronic analogue of succinate, is a suicide inactivator of succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1] as follows. (i) When rat liver mitochondria oxidize succinate in the presence of 3-nitropropionate carbanion, the rate of O2 consumption decreases exponentially to a zero value. This pattern is duplicated by subsequent additions of mitochondria. The dependence of the apparent first-order rate constant for enzyme inhibition, as well as the number of enzyme turnovers completed before inhibition, on the concentrations of 3-nitropropionate carbanion and succinate are those expected for an active site-directed and irreversible inhibitor. (ii) The inactivated enzyme is not resuscitated by centrifugation and washing of the mitochondria, in contrast to malonate-treated enzyme, and malonate protects against irreversible, inhibition. (iii) The inhibitor species is 3-nitropropionate carbanion and no external nucleophile is required for inhibition. (iv) The respiratory rates, respiratory control ratios, and ADP/O ratios obtained with NAD-linked substrates are unaffected by 3-nitropropionate carbanion. These results show that 3-nitropropionate carbanion is a highly specific, time-dependent, and irreversible inhibitor of succinate dehydrogenase. By analogy with the reaction of nitroethane with D-amino acid oxidase, the data are consistent with the hypothesis that the carbanionic inhibitor forms a covalent N-5 adduct with the active site flavin. 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.
Citation Manager Formats
More Articles of This Classification
Related Content
- No related articles found.
Cited by...
- Construction of a Recyclable Genetic Marker and Serial Gene Deletions in the Human Pathogenic Mucorales Mucor circinelloides
- The Combined Structural and Kinetic Characterization of a Bacterial Nitronate Monooxygenase from Pseudomonas aeruginosa PAO1 Establishes NMO Class I and II
- Multifunctional essentiality of succinate metabolism in adaptation to hypoxia in Mycobacterium tuberculosis
- Structural Basis for Malfunction in Complex II
- Involvement of the Up-regulated FoxO1 Expression in Follicular Granulosa Cell Apoptosis Induced by Oxidative Stress
- Geometric Restraint Drives On- and Off-pathway Catalysis by the Escherichia coli Menaquinol:Fumarate Reductase
- Growth of Bacteria on 3-Nitropropionic Acid as a Sole Source of Carbon, Nitrogen, and Energy
- Brain mitochondrial defects amplify intracellular [Ca2+] rise and neurodegeneration but not Ca2+ entry during NMDA receptor activation
- 3-Nitropropionic Acid Is a Suicide Inhibitor of Mitochondrial Respiration That, upon Oxidation by Complex II, Forms a Covalent Adduct with a Catalytic Base Arginine in the Active Site of the Enzyme
- Histone Deacetylase Inhibition by Sodium Butyrate Chemotherapy Ameliorates the Neurodegenerative Phenotype in Huntington's Disease Mice
- Neuronal Pyruvate Carboxylation Supports Formation of Transmitter Glutamate
- Mechanisms of Cell Death Induced by the Mitochondrial Toxin 3-Nitropropionic Acid: Acute Excitotoxic Necrosis and Delayed Apoptosis