The effect of inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase on TRH degradation in rat serum.
The identity of the enzymes catalyzing the degradation of thyrotropin releasing hormone (TRH) in rat serum was investigated by the use of specific inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase. These inhibitors did not protect TRH from degradation, but o-phenanthroline afforded significant protection. The participation of "thyroliberinase", a metalloenzyme which cleaves TRH at the pyroglutamyl-His bond was implied. A coupled assay using the chromogenic substrate pyroglutamyl-His-Pro-2-naphthylamide and excess diaminopeptidase IV was developed to specifically quantitate "thyroliberinase" activity. Rat serum catalyzed the degradation of 67.5 nmoles substrate/ml serum/h. The data indicate that TRH is degraded in rat serum predominantly by "thyroliberinase" and that prolyl endopeptidase and pyroglutamyl peptide hydrolase do not contribute significantly to this process.
Friedman
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Wilk
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D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D000818:Animals; D002863:Chromogenic Compounds / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism / Q000494:pharmacology; D018819:Dipeptidyl Peptidase 4; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000378:metabolism; D010450:Endopeptidases / Q000378:metabolism*; D008297:Male; D009842:Oligopeptides / Q000378:metabolism; D010618:Phenanthrolines / Q000494:pharmacology; D000085822:Prolyl Oligopeptidases; D011751:Pyroglutamyl-Peptidase I / Q000037:antagonists & inhibitors*; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains / Q000097:blood; D012697:Serine Endopeptidases; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D002863:Chromogenic Compounds; D004151:Dipeptides; D009842:Oligopeptides; D010618:Phenanthrolines; C049127:histidylprolyl-2-naphthylamide; D013973:Thyrotropin-Releasing Hormone; C049126:pyroglutamyl-histidyl-prolyl-2-naphthylamide; C038541:N-benzyloxycarbonylprolylprolinal; C046251:pyroglutamyl diazomethyl ketone; D010450:Endopeptidases; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4; D011751:Pyroglutamyl-Peptidase I; C023166:pyroglutamyl-peptidase II; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D011761:Pyrrolidonecarboxylic Acid; C025205:1,10-phenanthroline