title: Spodoptera littoralis detoxifies neurotoxic 3-nitropropanoic acid by conjugation with amino acids.
abstract: Spodoptera littoralis is a phytophagous generalist. Its host range includes more than 40 plant species, some of which produce 3-nitropropanoic acid (3-NPA), an irreversible inhibitor of mitochondrial succinate dehydrogenase. Growth in larvae fed an artificial diet with a sublethal admixture of 3-NPA (4.2 μmol per g) was slowed significantly, but larvae experienced no increase in mortality. In contrast, larvae injected with 25.2 μmol/g (bodyweight) 3-NPA experienced acute toxicity and death. To study the detoxification mechanism of 3-NPA in S. littoralis, the insect frass was analyzed by HPLC-MS. Comparative analysis of 3-NPA-treated and -untreated control samples using HR-MS(2) revealed a group of differential signals that were identified as amino acid amides of 3-NPA with glycine, alanine, serine, and threonine. When sublethal amounts of stable isotope-labeled 3-NPA were injected into a larva's hemolymph, 3-NPA amino acid conjugates were identified as putative detoxification products. Bioassays with synthetic standards confirmed that the toxicity of the amides was negligible in comparison to the toxicity of free 3-NPA, demonstrating that amino acid conjugation in S. littoralis represents an efficient way to detoxify 3-NPA. Furthermore, biosynthetic studies using crude fractions of the gut tissue indicated that conjugation of 3-NPA with amino acids occurs in epithelial cells of the insect's gut. Taken together, these results suggest that the detoxification of 3-NPA in S. littoralis proceeds via conjugation to specific amino acids within the epithelial cells followed by export of the nontoxic amino acid conjugates to the hemolymph via as yet uncharacterized mechanisms, most likely involving the Malpighian tubules.
authors.affiliation: Max Planck Institute for Chemical Ecology, Bioorganic Chemistry, Hans-Knoell-Straße 8, D-07745, Jena, Germany.
authors.forename: Alexey
authors.initials: A
authors.lastname: Novoselov
authors.affiliation: Max Planck Institute for Chemical Ecology, Bioorganic Chemistry, Hans-Knoell-Straße 8, D-07745, Jena, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Becker
authors.affiliation: Max Planck Institute for Chemical Ecology, Bioorganic Chemistry, Hans-Knoell-Straße 8, D-07745, Jena, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Pauls
authors.affiliation: Max Planck Institute for Chemical Ecology, Bioorganic Chemistry, Hans-Knoell-Straße 8, D-07745, Jena, Germany.
authors.forename: Stephan H
authors.initials: SH
authors.lastname: von Reuß
authors.affiliation: Max Planck Institute for Chemical Ecology, Bioorganic Chemistry, Hans-Knoell-Straße 8, D-07745, Jena, Germany. Electronic address: boland@ice.mpg.de.
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Boland
mesh_terms: D000577:Amides / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D041981:Gastrointestinal Tract / Q000378:metabolism; D006458:Hemolymph / Q000378:metabolism; D008658:Inactivation, Metabolic; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D009574:Nitro Compounds / Q000378:metabolism* / Q000633:toxicity; D011422:Propionates / Q000378:metabolism* / Q000633:toxicity; D018411:Spodoptera / Q000254:growth & development / Q000378:metabolism*
chemical_list: D000577:Amides; D000596:Amino Acids; D009574:Nitro Compounds; D011422:Propionates; C015392:3-nitropropionic acid
keywords: 3-Nitropropanoic acid; Amino acid conjugates; Detoxification; Metabolism; Spodoptera littoralis