Abstract
Synaptosomal membrane (SPM) bound exo- and endopeptidases cleave the dynorphins and Met-enkephalin-Arg-Gly-Leu at several sites to produce shorter fragments; among these are dynorphin 1–8 from 1–17, and Met-enkephalin from Metenkephalin-Agr-Gly-Leu. the most vulnerable site is the Tyr-Gly bond cleaved by membrane-bound aminopeptidase(s), with the shorter peptides degraded more rapidly than the longer ones. A purified metalloendopeptidase sensitive to phosphoramidon inactivates the shorter peptide sequences at the Gly3-Phe4 bond, and the 1–13 and 1–17 sequences also at the Arg7-Ile8 bond. The kcat/Km ratios for purified metalloendopeptidase were 20–30 times higher for Leu-enkephalin and the proenkephalin octapeptide than for dynorphins 1–8, 1–13, and 1–17. Dynorphins 1–13 and 1–17 may serve as precursors for the widely distributed CNS neuropeptide dynorphin 1–8 since they were cleaved by a separate SPM endopeptidase insensitive to phosphoramidon. SPM monocarboxypeptidase converted dynorphin 1–13 to 1–12 (release of Lys) and dipeptidyl carboxypeptidase converted dynorphin 1–8 to 1–6; enkephalin octapeptide served as a precursor of Met-enkephalin by sequential action (release of Leu and Arg-Gly) of both carboxypeptidases.
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Dedicated to Henry McIlwain.
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Benuck, M., Berg, M.J. & Marks, N. Membrane-bound enzymes and their role in processing of the dynorphins and of the proenkephalin octapeptide Met-enkephalin-Arg-Gly-Leu. Neurochem Res 9, 733–749 (1984). https://doi.org/10.1007/BF00965662
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DOI: https://doi.org/10.1007/BF00965662