| Title: | Succinylated octopamine ascarosides and a new pathway of biogenic amine metabolism in Caenorhabditis elegans |
| Author(s): | Artyukhin AB; Yim JJ; Srinivasan J; Izrayelit Y; Bose N; von Reuss SH; Jo Y; Jordan JM; Baugh LR; Cheong M; Sternberg PW; Avery L; Schroeder FC; |
| Address: | "Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA" |
| ISSN/ISBN: | 1083-351X (Electronic) 0021-9258 (Print) 0021-9258 (Linking) |
| Abstract: | "The ascarosides, small-molecule signals derived from combinatorial assembly of primary metabolism-derived building blocks, play a central role in Caenorhabditis elegans biology and regulate many aspects of development and behavior in this model organism as well as in other nematodes. Using HPLC-MS/MS-based targeted metabolomics, we identified novel ascarosides incorporating a side chain derived from succinylation of the neurotransmitter octopamine. These compounds, named osas#2, osas#9, and osas#10, are produced predominantly by L1 larvae, where they serve as part of a dispersal signal, whereas these ascarosides are largely absent from the metabolomes of other life stages. Investigating the biogenesis of these octopamine-derived ascarosides, we found that succinylation represents a previously unrecognized pathway of biogenic amine metabolism. At physiological concentrations, the neurotransmitters serotonin, dopamine, and octopamine are converted to a large extent into the corresponding succinates, in addition to the previously described acetates. Chemically, bimodal deactivation of biogenic amines via acetylation and succinylation parallels posttranslational modification of proteins via acetylation and succinylation of L-lysine. Our results reveal a small-molecule connection between neurotransmitter signaling and interorganismal regulation of behavior and suggest that ascaroside biosynthesis is based in part on co-option of degradative biochemical pathways" |
| Keywords: | "Adrenergic alpha-Agonists/chemistry Animals Behavior, Animal Biogenic Amines/*metabolism Caenorhabditis elegans/*metabolism Chromatography, High Pressure Liquid Dopamine/metabolism Glycosides/chemistry Mass Spectrometry Neurotransmitter Agents/metabolism;" |
| Notes: | "MedlineArtyukhin, Alexander B Yim, Joshua J Srinivasan, Jagan Izrayelit, Yevgeniy Bose, Neelanjan von Reuss, Stephan H Jo, Yeara Jordan, James M Baugh, L Ryan Cheong, Micheong Sternberg, Paul W Avery, Leon Schroeder, Frank C eng GM008500/GM/NIGMS NIH HHS/ DK83593/DK/NIDDK NIH HHS/ HHMI/Howard Hughes Medical Institute/ T32 GM008500/GM/NIGMS NIH HHS/ R01 DK083593/DK/NIDDK NIH HHS/ GM085285/GM/NIGMS NIH HHS/ R01 GM085285/GM/NIGMS NIH HHS/ GM088290/GM/NIGMS NIH HHS/ R01 GM088290/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2013/05/22 J Biol Chem. 2013 Jun 28; 288(26):18778-83. doi: 10.1074/jbc.C113.477000. Epub 2013 May 20" |
