Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

beta-Endorphin is converted into the biologically active fragment gamma-endorphin by an endopeptidase which we term "gamma-endorphin generating endopeptidase". Subcellular and regional distributions of this endopeptidase activity in rat brain were studied by a newly developed assay. After subcellular fractionation of rat brain tissue gamma-endorphin generating endopeptidase activity was predominantly recovered in the cytosolic fraction. A 10 to 15 fold lower activity was present in synaptosomes, mitochondria and synaptic membranes. Hardly any endopeptidase activity was detected in nuclei and myelin. The endopeptidase activity in cytosolic and particulate fraction was found throughout brain, pituitary and spinal cord in a rather homogeneous fashion. Cytosolic activity in all brain parts was 10 to 15 fold higher than the activity in the particulate fraction. It is suggested that rather the beta-endorphin distribution than the endopeptidase is restricting for gamma-endorphin production in certain brain parts.
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PMID:gamma-Endorphin generating endopeptidase in rat brain: subcellular and regional distribution. 257 53

Neutral endopeptidase (EC 3.4.24.11) is an integral membrane protein found at the plasma membrane of many cell types and is especially abundant at the apical "brush border" membrane of the kidney proximal tubules. The enzyme consists of a short amino-terminal cytosolic domain of 27 amino acids, a single hydrophobic sequence which is believed to be responsible for anchoring the enzyme in the plasma membrane, and a large extracellular domain containing the active site. This model is consistent with the proposed function of neutral endopeptidase, which is believed to play an important role in the inactivation of small regulatory peptides at the cell surface. Site-directed mutagenesis has allowed the identification of 1 glutamic acid and 2 histidine residues essential for catalysis. All are located near the COOH terminus of the protein. We do not know, however, whether other segments of the protein are involved in the structure of the active site. The exact role of the cytosolic and transmembrane domains is also unknown. In this report, we have induced the secretion of a soluble form of recombinant neutral endopeptidase in COS-1 cells by fusing in-frame, the cDNA encoding the signal peptide of a secreted protein (pro-opiomelanocortin) to the cDNA sequences of the complete ectodomain of neutral endopeptidase. Characterization of the secreted recombinant protein indicated that it has the same catalytic properties as the membrane-bound recombinant enzyme or as the enzyme extracted from kidney brush border membranes. Thus the extracellular domain alone is sufficient for conferring full catalytic activity to neutral endopeptidase.
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PMID:Fusion of a cleavable signal peptide to the ectodomain of neutral endopeptidase (EC 3.4.24.11) results in the secretion of an active enzyme in COS-1 cells. 267 Sep 43

Normal human pituitaries were extracted in boiling water and acetic acid, and the alpha-amidated peptide products of pro-opiomelanocortin (POMC), alpha-melanocyte-stimulating hormone (alpha MSH), gamma-melanocyte-stimulating hormone (gamma 1MSH), and amidated hinge peptide (HP-N), as well as their glycine-extended precursors, were characterized by sequence-specific radioimmunoassays, gel-chromatography, h.p.l.c. and amino acid sequencing. alpha MSH and gamma 1MSH constituted 0.27-1.32% and 0.10-5.10%, respectively, of the POMC-derived products [calculated as the sum of adrenocorticotropic hormone (ACTH)-(1-39), ACTH-(1-14) and alpha MSH immunoreactivity]. alpha MSH and ACTH-(1-14) were only present in non- or mono-acetylated forms. Only large forms of gamma 1MSH and gamma 2MSH were present in partly glycosylated states. The hinge peptides were amidated to an extent two to three orders of magnitude greater than alpha MSH and gamma 1MSH. Most (99%) of the HP-N was of low molecular mass and consisted mainly of HP-N-30. The remaining part was high-molecular-mass HP-N, probably HP-N-108, although the presence of HP-N-44 could not be completely excluded. These results show that all the possible amidated POMC-related peptides are present in normal human pituitary. It also shows that cleavage in vivo at all dibasic amino acids but one, takes place at the N-terminal POMC region; the exception is at the POMC-(49-50) N-terminal of the gamma MSH sequence. The pattern of peptides produced suggests that the generation of amidated peptides is mainly regulated at the endopeptidase level.
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PMID:Alpha-amidated peptides derived from pro-opiomelanocortin in normal human pituitary. 283 46

Vasopressin (VP)-converting aminopeptidase (VP-AP) activity and VP contents were measured in single rat pineal glands during the summer of two successive years. The peptidase activity decreased significantly in August. The lowest activity (+/- SEM) of 0.18 +/- 0.02 pmol.hour-1 was recorded on August 14, compared to the basal activity of 0.25 +/- 0.01 pmol.hour-1 in July and September of 1986. The change with similar percentage occurred in the same period of 1987. The specific activity of the enzyme in the crude homogenate, 15,000 g pellet and supernatant fraction of rat pineal glands, exhibited the same pattern of variations. The decrease in peptidase activity coincided with the previously reported dramatic rise in pineal VP content in early August which was confirmed in this series of experiments. Another peptidase, the so-called gamma-endorphin generating endopeptidase (gamma-EGE) activity, and beta-endorphin-related peptides in the pineal gland did not change in this period. The results show that the variations of pineal VP contents and VP-AP activity during summer are not general for other peptides and peptidases. The coincidence of opposite changes in VP content and VP-AP activity of the pineal gland may indicate a role of the peptidase activity to regulate the VP content.
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PMID:Changes in vasopressin-converting aminopeptidase activity in the rat pineal gland during summer: relationship to vasopressin contents. 297 42

The occurrence of intermediates from the processing of ACTH-(1-39) [adrenocorticotropic hormone-(1-39)] to alpha-melanocyte-stimulating hormone was investigated in normal pig pituitaries by the use of sensitive and specific radioimmunoassays for ACTH-(1-13), ACTH-(1-14), ACTH-(1-13)-NH2 and ACTH-(1-39). Fractionation by reverse-phase h.p.l.c. revealed ACTH(1-17) and their acetylated analogues. The intermediate lobe contained NO-diacetyl-ACTH-(1-13)-NH2, N-acetyl-ACTH-(1-13)-NH2 and ACTH-(1-13)-NH2. In addition, the corresponding ACTH-(1-14) peptides (the glycine-extended precursor of the amidated peptides) were detected in lower amounts in both the intermediate lobe and the anterior lobe. ACTH-(1-17), ACTH-(1-13) and their acetylated analogues could not be detected in the anterior lobe or the intermediate lobe. The results suggest that an endopeptidase initially cleaves ACTH-(1-39) at the Lys-16-Arg-17 bond. ACTH-(1-16) is then processed by a pituitary carboxypeptidase to ACTH-(1-14) and ACTH-(17-39) by the aminopeptidase to ACTH-(18-39).
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PMID:alpha-Melanocyte-stimulating-hormone precursors in the pig pituitary. 301 6

The endogenous opioid peptides all contain the enkephalin sequence Tyr-Gly-Gly-Phe-Met and Tyr-Gly-Gly-Phe-Leu at their aminoterminus. Three distinct families of these peptides (endorphins, enkephalins and dynorphins) are present in different neuronal pathways within the central nervous system. Molecular genetics have shown that these three families of opioid peptides are derived from three distinct precursors. Pro-opiomelanocortin gives rise to the endorphins, as well as adrenocorticotropic hormone (ACTH) and the melanotropic hormones (MSH's). [Met] enkephalin, [Leu] enkephalin and the related heptapeptide [Met] enkephalin-Arg6-Phe7 and octapeptide [Met] enkephalin-Arg6-Gly7-Leu8 are derived from proenkephalin. The third family is derived from prodynorphin and includes dynorphin A, dynorphin B (also known as rimorphin) and alpha- and beta-neo-endorphin. The structure of the genes coding for these precursors are similar, suggesting the possibility of one common ancestral gene. The most common scheme for enzymatic maturation of precursors proposes the action of a trypsin-like endopeptidase followed by a carboxypeptidase B-like exopeptidase. However, we have provided evidence that this combination of trypsin-like and carboxypeptidase B-like enzymes may not be the only mechanism for liberating enkephalin from low molecular weight enkephalin-containing peptides. Indeed, endo-oligopeptidase A, an enzyme, known to hydrolyze the Phe5-Ser6 bond of bradykinin and the Arg8-Arg9 bond of neurotensin, has been shown to produce, by a single cleavage, [Leu] enkephalin or [Met] enkephalin from small enkephalin-containing peptides, (Camargo et al., 1987, J. Neurochem. 48, 1258-1263).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Biosynthesis of opioid peptides]. 305 81

Endopeptidase-24.11, an ectoenzyme with a key role in metabolizing peptides at cell surfaces, is present in the adenohypophysis. A specific polyclonal antibody to the endopeptidase has been used to explore its localization in cryostat sections of pig pituitary glands by an immunoperoxidase method. Immunoreactivity was symmetrically but not uniformly distributed over the anterior lobe, with the highest intensity a zone just beneath the capsule along the anterior surface. In detail, the staining was observed to be in the cell membrane, but in some cells a small area of intense paranuclear staining was also observed. Serial 5 micron sections were immunostained alternately for endopeptidase-24.11 and for pituitary proteohormone. Luteinizing hormone (LH), follicular stimulating hormone (FSH), thyrotropin, adrenocorticotropin, prolactin and growth hormone were studied in this way. It was possible to identify groups of cells in adjacent sections and a good correlation was observed for endopeptidase-24.11-immunoreactivity with that for LH and FSH. The association of the endopeptidase with gonadotrophs was confirmed by double labelling. No evidence of colocalization was observed with the other proteohormone antibodies. We conclude that among the cells of the adenohypophysis only the gonadotrophs express endopeptidase-24.11 and discuss the possible significance of this observation in regard to the termination of peptide signals, such as that of luteinizing hormone-releasing hormone (LHRH) acting at this site.
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PMID:Endopeptidase-24.11 in the adenohypophysis of the pig is localized in the gonadotrophic cells. 316 48

Mammalian cell lines (BSC-40, NG108-15, and GH4C1) that cannot process the murine neuroendocrine peptide precursor prepro-opiomelanocortin (mPOMC) when its synthesis is directed by a vaccinia virus vector were coinfected with a second recombinant vaccinia virus carrying the yeast KEX2 gene, which encodes an endopeptidase that cleaves at pairs of basic amino acid residues. mPOMC was cleaved intracellularly to a set of product peptides normally found in vivo, including mature gamma-lipotropin and beta-endorphin1-31. In GH4C1 cells (a rat pituitary line), product peptides were incorporated into stored secretory granules. These results suggest that the inability of any particular cell line to process a prohormone precursor is due to the absence of a suitable endogenous processing enzyme.
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PMID:Yeast KEX2 endopeptidase correctly cleaves a neuroendocrine prohormone in mammalian cells. 329 Nov 17

Actinonin, previously isolated as an antibiotic and shown to be an inhibitor of aminopeptidase M (EC 3.4.11.2), has now been shown to inhibit three enkephalin-degrading enzymes from guinea-pig striatum. The values of IC50 were 0.39 microM for striatal membrane aminopeptidase ("enkephalin-aminopeptidase") and 5.6 microM striatal membrane neutral endopeptidase ("enkephalinase A"). Furthermore, soluble dipeptidylaminopeptidase in a rat whole brain homogenate was also inhibited by actinonin with the IC50 value of 1.1 microM. Actinonin administered intracisternally (i.cist., 50 micrograms) or intraperitoneally (i.p., 100 mg/kg), potentiated the analgesic action of met-enkephalin (50 micrograms i.cist.). analgesia by a tail-flick test. The potentiating activity of actinonin i.p. to met-enkephalin analgesia was almost the same potency as that of thiorphan, whereas the inhibitory activity of actinonin against enkephalinase A was 1/1000 that of thiorphan. Actinonin alone, administered either i.cist. or i.p., showed an analgesic action as estimated by the tail-flick test.
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PMID:Analgesic effect of actinonin, a new potent inhibitor of multiple enkephalin degrading enzymes. 329 9

1. Proline endopeptidase (E.C.3.4.21.26) is an enzyme which cleaves several peptides at the carboxyl side of proline residues. Because brain contains relatively large amounts of this enzyme and because of its specificity it has been suggested that it plays a role in the metabolism of neuropeptides, acting both on their processing and their degradation. 2. Since the final steps of neuropeptide processing occur in the synaptic vesicles and the degradation of most of these peptides is believed to occur in the synaptic cleft, we studied the distribution of proline endopeptidase activity in sub-fractions of rat hypothalamus. 3. Proline endopeptidase activity is present in synaptosomal fractions and is released by hypo-osmotic shock. Its specific activity is higher in the synaptoplasma than in synaptic membranes or vesicles (7.98 vs 0.18 and 0.24 nmol min-1 mg protein-1 carbobenzoxy-glycyl-prolyl-sulfamethoxazole hydrolysis). 4. Inhibitory avoidance training, a situation which releases hypothalamic vasopressin and beta-endorphin, both in vitro substrates, did not affect the specific or total activity of proline endopeptidase in synaptosomal plasma membranes.
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PMID:Distribution of proline endopeptidase activity in sub-synaptosomal fractions of rat hypothalamus. 330 57


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