Thyrotrophin releasing hormone degradation by rat synaptosomal peptidases: production of the metabolite His-Pro.
The dipeptide, His-Pro, is the major product of the degradation of TRH by rat synaptic membranes in vitro. A small amount of His-Pro is also formed from TRH by the synaptosomal soluble fraction. From inhibitor studies, the main route to His-Pro appears to involve removal of the pGlu residue by membrane-bound metal-dependent pyroglutamylaminopeptidase followed by deamidation. The deamidation step is not mediated by proline endopeptidase (EC3.4.21.26) nor dipeptidylpeptidase-IV (EC3.4.14.5) since it is insensitive to bacitracin and diprotin-A, and may therefore involve a novel membrane-bound TRH metabolizing enzyme. His-Pro is degraded rapidly by the soluble synaptosomal fraction, presumably by prolidase (EC3.4.13.9) and more slowly by the synaptic membrane fraction.
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D004150:Dipeptidases / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism*; D010450:Endopeptidases / Q000378:metabolism; D004791:Enzyme Inhibitors; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism*; D000085822:Prolyl Oligopeptidases; D011751:Pyroglutamyl-Peptidase I / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012697:Serine Endopeptidases; D013574:Synaptosomes / Q000201:enzymology*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D004151:Dipeptides; D004791:Enzyme Inhibitors; C035699:histidylproline; D013973:Thyrotropin-Releasing Hormone; D010450:Endopeptidases; D010447:Peptide Hydrolases; D004150:Dipeptidases; C022449:proline dipeptidase; D011751:Pyroglutamyl-Peptidase I; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases