{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363107369451715328.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.74.9.3767"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.74.9.3767"}},{"identifier":{"@type":"NAID","@value":"30016265704"}}],"dc:title":[{"@value":"3-Nitropropionate, the toxic substance of\n            <i>Indigofera</i>\n            , is a suicide inactivator of succinate dehydrogenase"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>\n            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. (\n            <jats:italic>i</jats:italic>\n            ) When rat liver mitochondria oxidize succinate in the presence of 3-nitropropionate carbanion, the rate of O\n            <jats:sub>2</jats:sub>\n            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. (\n            <jats:italic>ii</jats:italic>\n            ) 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. (\n            <jats:italic>iii</jats:italic>\n            ) The inhibitor species is 3-nitropropionate carbanion and no external nucleophile is required for inhibition. (\n            <jats:italic>iv</jats:italic>\n            ) 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\n            <jats:italic>Indigofera endecaphylla</jats:italic>\n            for mammals and fowl as being due to the irreversible blockage of the Krebs cycle by 3-nitropropionate carbanion.\n          </jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380013188215773825","@type":"Researcher","foaf:name":[{"@value":"Theodore A. Alston"}],"jpcoar:affiliationName":[{"@value":"Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188215773826","@type":"Researcher","foaf:name":[{"@value":"Leena Mela"}],"jpcoar:affiliationName":[{"@value":"Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104"},{"@value":"Harrison Department of Surgical Research, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104"}]},{"@id":"https://cir.nii.ac.jp/crid/1380013188215773824","@type":"Researcher","foaf:name":[{"@value":"Harold J. Bright"}],"jpcoar:affiliationName":[{"@value":"Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"1977-09","prism:volume":"74","prism:number":"9","prism:startingPage":"3767","prism:endingPage":"3771"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.74.9.3767"}],"createdAt":"2006-05-31","modifiedAt":"2022-04-13","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360004239457530880","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Spontaneous recovery of cochlear fibrocytes after severe degeneration caused by acute energy failure"}]},{"@id":"https://cir.nii.ac.jp/crid/1360306905179233152","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"SDHAF2 facilitates mitochondrial respiration through stabilizing succinate dehydrogenase and cytochrome c oxidase assemblies"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567187495468544","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Pharmacological Inhibition of Cochlear Mitochondrial Respiratory Chain Induces Secondary Inflammation in the Lateral Wall: A Potential Therapeutic Target for Sensorineural Hearing Loss"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848659845963904","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Recovery of endocochlear potential after severe damage to lateral wall fibrocytes following acute cochlear energy failure"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679749746176","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Cell therapy targeting cochlear fibrocytes"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679838040448","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Increased Expression of Osteopontin in the Degenerating Striatum of Rats Treated with Mitochondrial Toxin 3-Nitropropionic Acid: A Light and Electron Microscopy Study"}]},{"@id":"https://cir.nii.ac.jp/crid/1570854174921590912","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Human neural stem cells genetically modified for brain repair in neurological disorders"}]},{"@id":"https://cir.nii.ac.jp/crid/1572543024324899712","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Amyloid β protein inhibits cellular MTT reduction not by suppression of mitochondrial succinate dehydrogenase but by acceleration of MTT formazan exocytosis in cultured rat cortical astrocytes"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.74.9.3767"},{"@type":"CIA","@value":"30016265704"},{"@type":"CROSSREF","@value":"10.3389/fphar.2014.00198_references_DOI_UoM7RXfbPcctwsr3aF4CgI5R5Bk"},{"@type":"CROSSREF","@value":"10.1097/wnr.0000000000000673_references_DOI_UoM7RXfbPcctwsr3aF4CgI5R5Bk"},{"@type":"CROSSREF","@value":"10.1016/j.mito.2024.101952_references_DOI_UoM7RXfbPcctwsr3aF4CgI5R5Bk"},{"@type":"CROSSREF","@value":"10.1371/journal.pone.0090089_references_DOI_UoM7RXfbPcctwsr3aF4CgI5R5Bk"},{"@type":"CROSSREF","@value":"10.1267/ahc.15010_references_DOI_UoM7RXfbPcctwsr3aF4CgI5R5Bk"}]}