Article

Localization of a narrow-specificity thyroliberin hydrolyzing pyroglutamate aminopeptidase in synaptosomal membranes of guinea-pig brain.

European Journal of Biochemistry (Impact Factor: 3.58). 11/1984; 144(2):271-8.
Source: PubMed

ABSTRACT In this paper we report the presence of a particulate pyroglutamate aminopeptidase in guinea-pig brain tissue. This activity appears to reside in the synaptosomal membrane and could be released from the membrane by treatment with papain or Triton X-100. By contrast with a previously described broad-specificity soluble pyroglutamate aminopeptidase from guinea-pig brain tissue, the enzyme released from the synaptosomal membrane preparation removed pyroglutamic acid from thyroliberin, acid thyroliberin and less than Glu-His-Gly alone of the peptides tested. Unlike the soluble tissue enzyme the present enzyme was inhibited by the presence of EDTA and the activity released from synaptosomal membranes by papain was found to have a relative molecular mass of 230 000, almost one order of magnitude greater than that reported for the soluble enzyme.

0 Bookmarks
 · 
22 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The peptidergic signal substance TRH is inactivated by the TRH-degrading enzyme, a peptidase that exhibits a high degree of substrate specificity and other unusual characteristics. The tissue-specific regulation of the adenohypophyseal enzyme by estradiol and thyroid hormones suggests that it may serve an integrative function in modulating the response of adenohypophyseal target cells to TRH and thus pituitary hormone secretion. The high enzymatic activity of neuronal cells indicates that centrally this peptidase also might act as a terminator of neural TRH signals.
    Trends in Endocrinology and Metabolism 05/1995; 6(3):101-5. · 8.90 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effect of protein-modifying reagents on the activity of a purified preparation of a thyroliberin-hydrolysing pyroglutamate aminopeptidase, solubilised from synaptosomal membranes of guinea-pig brain by treatment with papain, was investigated. The results indicated that tyrosine, histidine, arginine, and possibly lysine residues were necessary for expression of catalytic activity and that these tyrosine, histidine, and arginine residues were probably located at the active site of the enzyme. Cysteine, serine, glutamate, and aspartate residues were not involved in the expression of catalytic activity.
    Journal of Neurochemistry 04/1987; 48(3):676-80. · 3.97 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    Journal of Neurochemistry 05/1986; 46(4):1231-9. · 3.97 Impact Factor