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)

A hypothesis was examined that carboxypeptidase H (CpAse H), which is known to catalyse the release of lysine and arginine from the C-terminus of peptides, can also release histidine, tyrosine, and phenylalanine. Synthetic peptides terminating in -His-Lys or -Tyr-Lys were used as model substrates for the enzyme and amino acid analysis was employed to detect release of the terminal amino acids. With N-acetyl-beta-Ala-Asn-Ala-His-Lys and N-acetyl-beta-Ala-Asn-Ala-Tyr-Lys, which correspond to intermediates in the processing of porcine and human beta-endorphin, lysine was removed rapidly and quantitatively but no release of histidine or tyrosine could be detected. To allow more sensitive analysis, radiolabelled substrates were employed and the amounts of the products formed on incubation with CpAse H were determined after separation by ion-exchange chromatography. With 125I-D-Tyr-Ala-His-Lys-Lys as substrate at pH 5.7, very small amounts of D-Tyr-Ala were released; the main product was D-Tyr-Ala-His. At pH 5.0 the release of histidine from 125I-D-Tyr-Ala-His took place 6,000 times more slowly than the release of lysine from 125I-D-Tyr-Ala-Lys. When the tripeptides were incubated at pH 5 with porcine pituitary secretory granules, the lysine was released rapidly but no release of histidine could be detected. The results demonstrate that CpAse H catalyses the release of C-terminal histidine with great difficulty.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Catalysis of slow C-terminal processing reactions by carboxypeptidase H. 252 98

The structure of alpha-melanocyte-stimulating hormone (alpha-MSH) has been determined in the pars intermedia of the frog Rana ridibunda. Pulse-chase labeling of frog neurointermediate lobes with selective amino acids revealed that the composition of frog alpha-MSH is similar to that of alpha-MSH from all mammalian species yet studied. Tryptic mapping of nexly synthetized alpha-MSH generated two fragments with the following amino acid composition: (T1) Trp, Pro, Lys, Gly, Val and (T2) Tyr, Arg, Phe, His, Ser, Glu. Concurrently, alpha-MSH was purified from 100 neurointermediate lobes to apparent homogeneity by reverse-phase HPLC. The sequence of the peptide determined by automated Edman degradation was Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val. The structure of frog alpha-MSH is thus identical to mammalian des-N alpha-acetyl alpha-MSH and differs from the sequence of toad (Xenopus laevis) alpha-MSH only by the first residue (Ser instead of Ala). These results confirm that the sequence of alpha-MSH has been highly preserved during evolution.
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PMID:Melanin concentrating hormone. V. Isolation and characterization of alpha-melanocyte-stimulating hormone from frog pituitary glands. 255 47

Novel D-amino acid modified, hexapeptide inhibitors of alpha-melanocyte-stimulating hormone (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2, alpha-MSH) are described. The discovery of the alpha-MSH inhibitory activity of a known somatotropin (growth hormone) secretagogue, H-His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 ([His1, Lys6-]GHRP, I), and its chemical similarity to the alpha-MSH6-11 sequence provided the impetus to investigate the structure-activity relationships of MSH-GHRP hybrid analogues. In this study we compared the melanotropic activity of a series of peptides of the generic formula H-His-Xaa-Yaa-Trp-D-Phe-Lys-NH2 (H-[Xaa7, Yaa8, D-Phe10] alpha-MSH6-11-NH2) on the R. pipiens (frog) and A. carolinensis (lizard) skin in vitro bioassays. In summary, D-Phe7-Ala8 substitution (II) in the heptapeptide template yielded an MSH-like agonist of moderately low potency (EC50 ca. 10(-6) M) relative to alpha-MSH; D-Ala7-Ala8 substitution (III) abolished agonist or antagonist activity. alpha-MSH inhibition was effected by MSH-GHRP analogues having D-Trp7-Ala8, D-Arg7-Ala8, D-Trp7-Arg8 or Phe7-Arg8 substitutions. The D-Trp7-Ala8 and Phe7-Arg8 modified derivatives (I and VI) selectively inhibited alpha-MSH on the R. pipiens assay (pA2 = 4.7 and 5.8, respectively), as they did not possess antagonist (or agonist) activities on the A. carolinensis assay. In contrast, the D-Arg7-Ala8 and D-Trp7-Arg8 modified derivatives (IV and V) inhibited alpha-MSH on both the R. pipiens and A. carolinensis assays (pA2 values ranging 5.0-6.0).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Discovery and structure-activity relationships of novel alpha-melanocyte-stimulating hormone inhibitors. 256 82

A novel neuropeptide which stimulates adenylate cyclase in rat anterior pituitary cell cultures was isolated from ovine hypothalamic tissues. Its amino acid sequence was revealed as: His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr-Ser-Arg-Tyr-Arg-Lys-Gln- Met-Ala- Val-Lys-Lys-Tyr-Leu-Ala-Ala-Val-Leu-Gly-Lys-Arg-Tyr-Lys-Gln-Arg-Val-Lys-Asn-Lys - NH2. The N-terminal sequence shows 68% homology with vasoactive intestinal polypeptide (VIP) but its adenylate cyclase stimulating activity was at least 1000 times greater than that of VIP. It increased release of growth hormone (GH), prolactin (PRL), corticotropin (ACTH) and luteinizing hormone (LH) from superfused rat pituitary cells at as small a dose as 10(-10)M (GH, PRL, ACTH) or 10(-9)M (LH). Whether these hypophysiotropic effects are the primary actions of the peptide or what physiological action in the pituitary is linked with the stimulation of adenylate cyclase by this peptide remains to be determined.
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PMID:Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. 280 20

A 34-amino acid peptide and three other structurally related peptides were isolated from rabbit fetal and adult lung. These cationic arginine- and cysteine-rich peptides inhibit corticotropin (ACTH)-stimulated rat adrenal cell corticosterone production. The peptide was called corticostatin (CSI). CSI was purified by reverse-phase HPLC and was shown to be homogenous from its amino acid analysis. Its sequence was determined on a gas-phase sequenator. The structure of CSI is Gly-Ile-Cys-Ala-Cys-Arg-Arg-Arg-Phe-Cys-Pro-Asn-Ser-Glu-Arg-Phe-Ser-Gly- Tyr-Cys - Arg-Val-Asn-Gly-Ala-Arg-Tyr-Val-Arg-Cys-Cys-Ser-Arg-Arg. CSI was found to markedly inhibit ACTH-stimulated corticosterone production by rat adrenal cells in vitro but did not affect basal levels. CSI did not affect the stimulation of aldosterone synthesis by angiotensin II in rat zona glomerulosa cells but it did suppress ACTH-stimulated aldosterone synthesis in whole adrenal cells, demonstrating that CSI is a specific inhibitor of ACTH-stimulated corticosteroid synthesis. The minimum effective concentration of CSI inhibiting ACTH-stimulated (33 pM) corticosterone production was 5 nM (20 ng/ml), the ED50 (50% effective dose) was 25 nM and steroidogenesis was completely inhibited at concentrations greater than 500 nM (2 micrograms/ml).
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PMID:Isolation and structure of corticostatin peptides from rabbit fetal and adult lung. 282 94

N alpha-Acetyltransferase, which catalyzes the transfer of an acetyl group from acetyl coenzyme A to the alpha-NH2 group of proteins and peptides, was isolated from Saccharomyces cerevisiae and demonstrated by protein sequence analysis to be NH2-terminally blocked. The enzyme was purified 4,600-fold to apparent homogeneity by successive purification steps using DEAE-Sepharose, hydroxylapatite, DE52 cellulose, and Affi-Gel blue. The Mr of the native enzyme was estimated to be 180,000 +/- 10,000 by gel filtration chromatography, and the Mr of each subunit was estimated to be 95,000 +/- 2,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme has a pH optimum near 9.0, and its pI is 4.3 as determined by chromatofocusing on Mono-P. The enzyme catalyzed the transfer of an acetyl group to various synthetic peptides, including human adrenocorticotropic hormone (ACTH) (1-24) and its [Phe2] analogue, yeast alcohol dehydrogenase I (1-24), yeast alcohol dehydrogenase II (1-24), and human superoxide dismutase (1-24). These peptides contain either Ser or Ala as NH2-terminal residues which together with Met are the most commonly acetylated NH2-terminal residues (Persson, B., Flinta, C., von Heijne, G., and Jornvall, H. (1985) Eur. J. Biochem. 152, 523-527). Yeast enolase, containing a free NH2-terminal Ala residue, is known not to be N alpha-acetylated in vivo (Chin, C. C. Q., Brewer, J. M., and Wold, F. (1981) J. Biol. Chem. 256, 1377-1384), and enolase (1-24), a synthetic peptide mimicking the protein's NH2 terminus, was not acetylated in vitro by yeast acetyltransferase. The enzyme did not catalyze the N alpha-acetylation of other synthetic peptides including ACTH(11-24), ACTH(7-38), ACTH(18-39), human beta-endorphin, yeast superoxide dismutase (1-24). Each of these peptides has an NH2-terminal residue which is rarely acetylated in proteins (Lys, Phe, Arg, Tyr, Val, respectively). Among a series of divalent cations, Cu2+ and Zn2+ were demonstrated to be the most potent inhibitors. The enzyme was inactivated by chemical modification with diethyl pyrocarbonate and N-bromosuccinimide.
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PMID:Purification and characterization of an N alpha-acetyltransferase from Saccharomyces cerevisiae. 284 92

The purpose of this study was to compare the binding potency to opioid receptors of met-enkephalin-derived, hypophysiotrophic peptides with their reported growth hormone (GH)-releasing strengths in vitro and further, to determine the relative selectivity of each peptide for mu and delta opioid binding sites in the forebrain of the rat. A series of (GH)-releasing pentapeptides and hexapeptides (GHRP's), as well as rat (rGHRH) and human (hGHRH) growth hormone-releasing hormones were tested for preferential binding to specific opioid receptors. The site selectivity of each peptide was determined by its ability to compete for binding with synthetic ligands for mu (Tyr-D-Ala-Gly-MePhe-Gly-ol; DAGO) and delta ([D-Pen2,5]-enkephalin; DPDPE) opioid receptors. The various peptides differed in their selectivities for the two opioid receptors in that most of the GHRP's were mu-selective, while the naturally occurring GHRH's were delta-selective. Amidation of the C-terminal decreased delta selectivity. Besides affecting selectivity for the site, structural changes that enhanced GH-release by enkephalin-derived peptides also decreased their potency to compete for opioid binding sites. For example, dose-response curves for His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (SK&F 110679) inhibition of the binding of DAGO and DPDPE yielded IC50's of 6 and 20 microM, respectively. In contrast, Tyr-D-Trp-Gly-Phe-Met-NH2 (BI360), which is 1 X 10(3) times weaker than SK&F 110679 in releasing GH, had IC50's of 0.1 microM and 0.08 microM for inhibition of the binding of DAGO and DPDPE, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Binding of growth hormone-releasing hormones and enkephalin-derived growth hormone-releasing peptides to mu and delta opioid receptors in forebrain of rat. 285 11

Beta-endorphin immunoreactivity was measured in plasma and hypothalamus of rats treated with alpha-methyl-p-tyrosine (alpha -MT) (two doses of 200 mg/kg) or p-chloro-phenyl-alanine (PCPA) (two doses of 150 mg/kg). It was also measured in plasma after a single dose (5 mg/kg) of amphetamine or after electrical stimulation of median raphe nucleus (MRN). Plasma levels of immunoreactive beta-endorphin (ir B-E) were significantly decreased by PCPA and were elevated by electrical stimulation of MRN. Alpha -MT was ineffective to modify ir B-E plasma concentration as well as amphetamine. These findings suggest a role for 5-hydroxytryptamine (5-HT) in the regulation of plasma B-E content.
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PMID:Involvement of a serotonergic control in the regulation of plasma levels of immunoreactive beta-endorphin. 287 72

The present study aimed at evaluating the effect of human beta-endorphin on pancreatic hormone levels and on glucose metabolism in normal subjects. Infusion of 143 nmol/h beta-endorphin in 7 subjects caused a significant rise in plasma glucose concentrations (+ 1.7 +/- 0.3 mmol/l) which was preceded by a significant increase in peripheral plasma glucagon levels (+ 44 +/- 13 ng/l). No changes occurred in the plasma concentrations of insulin and catecholamines (adrenaline and noradrenaline). The influence of beta-endorphin per se on glucose homeostasis was studied in 7 other subjects using the euglycaemic clamp technique in which the endocrine pancreatic function was fixed at its basal level with somatostatin together with replacement of basal insulin and glucagon by the exogenous infusion of these hormones. In this new metabolic conditions, beta-endorphin failed to have significant influences on the various parameters of tracer-estimated glucose metabolism (production, utilization, and clearance) and on the plasma levels of the gluconeogenic precursors (glycerol and alanine). Moreover, the levels of pancreatic and counterregulatory hormones (cortisol and catecholamines) were not different between beta-endorphin and control studies. We conclude that the naturally occurring opioid peptide beta-endorphin produced an hyperglycaemic effect in man which appears to be mediated by glucagon. The opioid seems to have no direct effect on glucose metabolism. These results suggest that the metabolic effects of beta-endorphin in normal man are secondary to its impact on pancreatic hormone secretion and not a consequence of a direct modulation of glucose metabolism.
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PMID:Primary role of glucagon release in the effect of beta-endorphin on glucose homeostasis in normal man. 288 94

The Saccharomyces cerevisiae secretory process was studied by evaluating secretion efficiency, processing efficiency, and the efficiency of protein folding for hybrid proteins containing the yeast prepro-alpha-factor leader region. Secretion of three proteins, beta-endorphin, calcitonin, and a consensus alpha-interferon (IFN-Con1), were compared in terms of secretion efficiency into the culture medium, beta-Endorphin and calcitonin, both small proteins, were found to be efficiently secreted from logarithmically grown cells. In contrast, the larger IFN-Con1 accumulated in the periplasmic space and cell wall. The glycosylated, unprocessed prepro-alpha-factor/IFN-Con1 fusion protein was also found to be secreted into the culture medium. The presence of (Glu-Ala) dipeptides in the alpha-factor spacer peptide increased the efficiency of cleavage at Lys-Arg in the prepro-alpha-factor/IFN-Con1 protein fusion. Purified secreted IFN-Con1 was structurally characterized to determine the effect of passage through the yeast secretory pathway on the fidelity and efficiency of protein folding. The disulfide structure of the secreted protein was found to be identical with that reported for the native human alpha-interferons.
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PMID:Protein secretion from Saccharomyces cerevisiae directed by the prepro-alpha-factor leader region. 300 32


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