Delineation of a particulate thyrotropin-releasing hormone-degrading enzyme in rat brain by the use of specific inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase - PubMed (original) (raw)

Delineation of a particulate thyrotropin-releasing hormone-degrading enzyme in rat brain by the use of specific inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase

T C Friedman et al. J Neurochem. 1986 Apr.

Abstract

The degradation of thyrotropin-releasing hormone in rat brain homogenates was studied in the presence of N-benzyloxycarbonyl-prolyl-prolinal and pyroglutamyl diazomethyl ketone, specific and potent active-site-directed inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase, respectively. Substantial TRH degradation was observed, suggesting the presence of another thyrotropin-releasing hormone-degrading enzyme(s). Reports of a thyrotropin-releasing hormone-degrading enzyme with narrow specificity that cleaves the pGlu-His bond of this tripeptide led us to develop a coupled assay using pGlu-His-Pro-2NA as the substrate to measure this activity. Cleavage of the pGlu-His bond of this substrate under conditions in which pyroglutamyl peptide hydrolase is not expressed occurred in the particulate fraction of a rat brain homogenate. This particulate pyroglutamyl-peptide cleaving enzyme was not inhibited by pyroglutamyl diazomethyl ketone but was inhibited by metal chelators such as EDTA and o-phenanthroline. The particulate pyroglutamyl-peptide cleaving enzyme was found predominantly in the brain. Activity in brain regions varied widely with highest levels present in cortex and hippocampus and very low levels in pituitary. The data suggest that degradation of thyrotropin-releasing hormone by the particulate fraction of a brain homogenate is catalyzed mainly by an enzyme that cleaves the pGlu-His bond of thyrotropin-releasing hormone but is distinct from pyroglutamyl peptide hydrolase.

PubMed Disclaimer

Cited by

Regulation of adenohypophyseal pyroglutamyl aminopeptidase II activity by thyrotropin-releasing hormone and phorbol esters.
Vargas MA, Cisneros M, Joseph-Bravo P, Charli JL. Vargas MA, et al. Endocrine. 2000 Dec;13(3):267-72. doi: 10.1385/endo:13:3:267. Endocrine. 2000. PMID: 11216637
Intrauterine Zn Deficiency Favors Thyrotropin-Releasing Hormone-Increasing Effects on Thyrotropin Serum Levels and Induces Subclinical Hypothyroidism in Weaned Rats.
Alcántara-Alonso V, Alvarez-Salas E, Matamoros-Trejo G, de Gortari P. Alcántara-Alonso V, et al. Nutrients. 2017 Oct 18;9(10):1139. doi: 10.3390/nu9101139. Nutrients. 2017. PMID: 29057835 Free PMC article.
Pyroglutamyl peptidase type I from Trypanosoma brucei: a new virulence factor from African trypanosomes that de-blocks regulatory peptides in the plasma of infected hosts.
Morty RE, Bulau P, Pellé R, Wilk S, Abe K. Morty RE, et al. Biochem J. 2006 Mar 15;394(Pt 3):635-45. doi: 10.1042/BJ20051593. Biochem J. 2006. PMID: 16248854 Free PMC article.
Kinetics and pattern of degradation of thyrotropin-releasing hormone (TRH) in human plasma.
Møss J, Bundgaard H. Møss J, et al. Pharm Res. 1990 Jul;7(7):751-5. doi: 10.1023/a:1015875824238. Pharm Res. 1990. PMID: 2118634

Delineation of a particulate thyrotropin-releasing hormone-degrading enzyme in rat brain by the use of specific inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase - PubMed (original) (raw)