Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetylated derivatives of glucagon have been prepared by reacting this hormone under various conditions with acetic anhydride. They have been chemically characterized by the use of a 14C-labeled reagent, by peptide mapping techniques following hydrolysis by pronase and chymotrypsin, and by spectroscopy. Acetylation in sodium acetate (pH 5.5) results in a full substitution of the alpha-amino group of the N-terminal histidyl residue, but in a partial (about 0.3 acetyl group per residue) substitution of the epsilon-amino group of the lysyl residue 12. The monosubstituted (on the alpha-amino group) and the disubstituted (on both amino groups) acetylated components have been separated by chromatography on DEAE-cellulose and CM-cellulose. Acetylation in sodium bicarbonate (pH 8.0) results in a complete substitution of both amino groups and of the hydroxyl groups of the tyrosyl residues 10 and 13. Complete deacetylation of the O-acetyltyrosyl residues occurs upon treatment with hydroxyl-amine. Mono, di and tetraacetylglucagon are homogeneous when analyzed by disc gel electrophoresis; di and tetrasubstituted derivatives show an increased mobility towards the anode. 125I-labeled derivatives of acetylglucagon show higher distribution coefficients in the aqueous two-phase dextran/poly(ethylene glycol) system than do similar derivatives of glucagon. Acetylation decreases in parallel the ability of glucagon to stimulate the activity of adenylate cyclase and to bind to its receptors in liver cell membranes of the rat. The biological potencies of the mono, di and tetrasubstituted derivates are, respectively, about 10, 1 and 0.1% that of native glucagon. The binding properties of the material dissociated from the acetylglucagon-receptor complex suggest that the reduction in biological activity results from a decrease in the intrinsic affinity of the modified glucagon for the receptors, as well as from the presence of small amounts of residual, unreacted glucagon. Studies with 125I-labeled derivatives of glucagon indicate that acetylation decreases the rate of association and increases the rate of dissociation of the hormone-receptor complex.
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PMID:Acetylglucagon: preparation and characterization. 0 Dec 70

Exocrine pancreatic function was investigated by means of the Lundh test model in dogs with chronic duodenal and gastric fistulas. The test was standardized and the effect of glucagon on exocrine pancreatic secretion was evaluated. The mean tryptic activity detected in 18 tests in 6 dogs was 32.25 +/- 5.25 muEqH+/minute/ml, which is considerably higher than that observed in man. The administration of glucagon was followed by a significant decrease (30.8%) in the volume of the duodenal contents and a more pronounced depression of the enzyme concentrations (trypsin 59%, chymotrypsin 53.3%). It is concluded that the Lundh test affords a valuable experimental model for the investigation of exocrine pancreatic function in dogs.
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PMID:Influence of glucagon on exocrine pancreatic function as determined by the Lundh test in dogs. 59 92

Enteropeptidase, trypsin, and chymotrypsin activity in basal and secretin-stimulated duodenal juice of 20 normal adult volunteers and 15 patients with gastrotestinal disease were determined. All enzyme concentrations showed skew distributions, but fluctuations in the secretin-stimulated juices were less pronouced than in the basal secretions. Secretin administration had no influence on the release of enteropeptidase from human duodenal mucosa, but resulted in a very small increase in secretion of pancreatic enzymes. Six out of seven patients with chronic alcoholic pancreatitis or cancer of the pancreas exhibited highly significant elevations of enteropeptidase in their basal as well as secretin-stimulated duodenal juice. It is suggested that raised luminal enteropeptidase activity may be the result of pancreatic insufficiency or elevated blood glucagon concentrations.
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PMID:Enteropeptidase levels in duodenal juice of normal subjects and patients with gastrointestinal disease. 66 28

The selective cleavage of peptide bonds by a serine protease from skeletal muscle (SK-protease) was examined using glucagon and neurotensin as substrates. Among the peptide bonds cleaved in these substrates, the most susceptible were Phe-Thr-Ser, Tyr-Leu, Trp-Leu, and Tyr-Ile. These results indicate that the SK-protease hydrolyzed the carboxyl side of aromatic amino acid residues under the experimental conditions. When the amino acid on the carboxyl side of aromatic amino acid residues was serine, threonine or glutamic acid, these peptide bonds, such as Phe-Thr, Tyr-Ser, and Tyr-Glu, were not susceptible to another serine protease from small intestine (SI-protease) under the same experimental conditions. The peptide bond between the arginines of Pro-Arg-Arg-Pro in neurotensin was hydrolyzed by the SI-protease, but not by the SK-protease. Thus the specificity of the SK-protease differs from that of the SI-protease. These results suggest that the specificity of the hydrolytic action of the SK-protease is more like that of bovine chymotrypsin A than like that of porcine chymotrypsin C and of the SI-protease.
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PMID:Selective cleavage of peptide bonds by a serine protease from rat skeletal muscle. 70 Dec 36

1. An anionic and a cationic chymotrypsin (EC 3.4.21.1) were isolated from the pancreas glands of the moose (Alces alces) and elk (Cervus elaphus). The A and B chymotrypsins from each species were purified to homogeneity by (NH4)2SO4 fractionation, affinity chromatography on 4-phenylbutylamine-Sepharose and ion-exchange chromatography on DEAE- and CM-cellulose. 2. The molecular weight and pH optimum of each chymotrypsin were similar to those of the corresponding ox A and B chymotrypsins. 3. The substrate specificities of the chymotrypsins were investigated by digestion of glucagon and the oxidized B chain of insulin. The primary specificity of each chymotrypsin for aromatic amino acid residues was further established by determining the Km and kcat for the hydrolysis of a number of synthetic amino acid ester substrates. 4. The amino acid composition and total number of residues of moose and elk chymotrypsin A were similar to those of ox chymotrypsin A. An even greater similarity was observed among the B chymotrypsins of the three species. 5. The A chymotrypsins of moose and elk were fragmented to their constituent 'A', 'B' and 'C' polypeptide chains by succinylation (3-carboxypropionylation), reduction and alkylation of the native enzymes. In each case, the two major chains ('B' and 'C') were separated and isolated. By comparison of the amino acid compositions of moose, elk and oxy 'B' and 'C' chains, a greater difference was observed among the three A chymotrypsins than was suggested by the amino acid compositions of the native enzymes alone. 6. Peptides were isolated from the disulphide bridge and active-site regions of the A and B chymotrypsins of moose and elk by diagonal peptide-'mapping' techniques. From the amino acid compositions of the isolated peptides (assuming maximum homology) and from a comparison of diagonal peptide 'maps', there was established a high degree of primary-structure identity among the mooae, elk and ox chymotrypsins. Tentative sequences were deduced for the peptides isolated by diagonal peptide 'mapping'. 7. Details of the isolation procedures of the moose and elk chymotrypsins A and B and the amino acid analyses of some peptides obtained by diagonal peptide 'mapping' have been deposited as Supplementary Publication SUP 50064 (27 pages) at the British Library Lending Division, Boston Spa, Wetherby, W. Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1976) 153, 5.
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PMID:Chymotrypsins from the deer (Cervidae) family. Isolation, partial characterization and primary-structure studies of chymotrypsins A and B from both moose (Alces alces) and elk (Cervus elaphus) pancreas. 94 18

Cells of Acinetobacter calcoaceticus contain a constitutive periplasmic metalloproteinase showing similar properties as the periplasmic metalloproteinase of Escherichia coli. The periplasmic proteinase of A. calcoaceticus was purified, starting from periplasm, by ammonium sulfate precipitation, hydrophobic interaction chromatography and chromatofocusing up to the homogeneity of the enzyme in SDS-electrophoresis with a yield of 6.7% and a purification factor of 417. The enzyme has a molecular mass of 108,000 (gel filtration) or 112,000 (native electrophoresis), and consists of four identical subunits with a molecular mass of 27,000 (SDS-electrophoresis). The purified enzyme degrades preferentially polypeptides such as glucagon and insulin. Larger proteins are accepted as substrates to a considerably lower extent. All tested synthetic substrates with trypsin, chymotrypsin, elastase and thermolysin specificity were not cleaved. Therefore, the described enzyme was designated "insulin-cleaving proteinase" (ICP).
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PMID:Purification of a periplasmic insulin-cleaving proteinase from Acinetobacter calcoaceticus. 151 May 71

Vasoactive intestinal peptide (VIP) is a neuropeptide with a broad range of biological activities in various tissues. After interaction with its membrane receptor, VIP generally induces a very large increase in the intracellular cyclic AMP level. Receptors for VIP have been described in numerous tissues and cell lines. The first results on VIP receptor structure have been obtained by covalent cross-linking using bifunctional reagents. The molecular mass of the different components characterized in this way differs greatly according to the species and the tissue used. This heterogeneity may reflect either a difference in the length of the cross-linked polypeptide backbone or differently glycosylated forms of the same polypeptide. The VIP binding site of intact human adenocarcinoma cells (HT29 cells) is an Mr 64,000 glycoprotein with 20kDa of N-linked oligosaccharide side chains containing sialic acid. The structure of the VIP binding site from HT29 cell is compared, first to the structure of the VIP receptor from other tissues, particularly that from rat liver, and second to the structure of the hepatic glucagon binding site. Recently, solubilization of the VIP receptor in an active form has provided a new way of studying this receptor. The HT29 cell line is an appropriate model to study the dynamics of the VIP receptor. After binding to its receptor, VIP is rapidly internalized, probably by receptor-mediated endocytosis. This internalization leads to a decrease in the cell surface receptor number and simultaneously to a homologous desensitization of adenylate cyclase. VIP is then degraded in the lysosomes, while most of the receptors are recycled back to the cell surface. The presence of an intracellular pool of unoccupied VIP receptors has been demonstrated after inactivation of the cell surface receptors by chymotrypsin. The kinetics of the receptor reappearance at the cell surface, after inactivation by chymotrypsin or after receptor-mediated endocytosis, indicate 2 possible intracellular pathways for occupied and unoccupied VIP receptors.
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PMID:The vasoactive intestinal peptide (VIP) receptor: recent data and hypothesis. 285 63

A saponin fraction was isolated from Momordica charantia seeds by delipidation, saline extraction, ammonium sulfate precipitation, and extraction of the resulting supernatant with n-butanol. Thin-layer chromatography, in the upper phase of the n-butanol--ethyl acetate--water (4:1:5, by volume) system on plastic sheets coated with silica gel 60 F254, revealed the presence of a single spot after spraying with 10% sulfuric acid. The lack of contamination of the saponin preparation with proteins was judged by the absence of protein bands in sodium dodecyl sulfate--polyacrylamide gel electrophoresis, agarose electrophoresis and agarose diffusion, and by the absence of an absorption maximum around 278 nm. The saponin acted as a noncompetitive inhibitor of corticotropin, glucagon, and epinephrine in lipolysis in isolated rat adipocytes, and it also antagonized dibutyryl cAMP induced lipolysis. The antilipolytic activity was resistant to heat, trypsin, chymotrypsin, pronase, and glutathione, in keeping with the chemical nature of saponin. Incorporation of [3-3H]glucose into lipid was inhibited. Adipocyte viability and ATP content were not affected by the saponin, suggesting that its inhibitory effects on lipolysis and lipogenesis were not due to an adverse effect on cell viability.
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PMID:A steryl glycoside fraction from Momordica charantia seeds with an inhibitory action on lipid metabolism in vitro. 302 Nov 85

Cathepsin-D has been previously reported to cleave intact PTH into PTH-(1-34) and -(35-84) in membranous fractions of rat and bovine kidney. Whether PTH degradation occurs by intact kidney cells, however, has not been examined in detail. We have, therefore, examined this possibility using an opossum kidney (OK) cell line which possesses the characteristics of proximal renal tubules and responds to PTH. PTH radioimmunoreactivity recovered in trichloroacetic acid-soluble products and in fractions eluted from reverse phase HPLC was measured using an antibody directed to the midregion and C-terminus of PTH. In this study, intact OK cells, but not extracellular enzymes, cleaved human (h) PTH-(1-84) into three discrete fragments which were released into the medium in a time- and temperature-dependent fashion. Half-maximal velocity of PTH-degrading activity (PTHDA) was observed at 9 nM hPTH-(1-84). A 1000-fold molar excess of PTH antagonists [hPTH-(3-34) and [Tyr34]hPTH-(7-34)amide] markedly inhibited PTHDA, whereas ACTH, glucagon, or big gastrin did not suppress it, suggesting an involvement of the PTH receptor in PTHDA. This PTHDA was strongly inhibited by phenylmethylsulfonylfluoride and chymostatin, but not by trypsin inhibitor, elastatinal, or inhibitors of aspartic, cysteine, or metalloproteinases, suggesting that it is due to a seryl chymotrypsin-like endopeptidase. Analysis of chymotrypsin-digested products of hPTH-(1-84) eluted from HPLC exhibited five fragments detected by UV absorbance (210 nm), three of which were measurable by PTH RIA, and each corresponded to the three PTH fragments produced by OK cells. All three fragments were predominantly suppressed in the presence of chymostatin, suggesting that chymotrypsin-like activity is solely responsible for PTHDA in intact OK cells. To further explore the cleavage sites of PTH by chymotrypsin, amino acid analysis of chymotrypsin-cleaved products was performed. The results strongly support the conclusion that a chymotrypsin-like enzyme in OK cells cleaved the hormone between residues 23-24, and 34-35 to produce, at least, hPTH-(24-84) and -(35-84). Lysosomal blockers (chloroquine, ammonium chloride, or monensin) did not affect this PTHDA. Our present study indicates that chymotrypsin-like endopeptidase, but not other endopeptidase or lysosomal enzymes, is responsible for the limited hydrolysis of PTH by intact OK cells.
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PMID:Parathyroid hormone degradation by chymotrypsin-like endopeptidase in the opossum kidney cell. 305 60

The effects of micelles of nonionic, zwitterionic, anionic and cationic surfactants and lipids on the conformation of glucagon and insulin have been investigated by circular dichroism and intrinsic protein fluorescence. The influence of these amphipathic compounds on the hydrolysis, monitored by HPLC, of glucagon and insulin by trypsin and chymotrypsin has also been studied. The alpha-helix content of glucagon was increased to a similar extent by all the micelles, irrespective of their charge and of whether they were synthetic surfactants or phospholipids. The amphipathic compounds always induced a blue-shift in the wavelength of maximum emission of fluorescence of glucagon of about 9 nm, whereas the fluorescence intensity was increased in some cases and decreased in others. The circular dichroism of insulin was also modified in some cases. Some amphipathic compounds protected glucagon against proteolysis by trypsin and chymotrypsin very markedly, whereas others did not protect at all or only slightly protected the hormone. Two hypotheses have been formulated to explain the different results. Hydrolysis of insulin was generally not influenced by surfactants and lipids.
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PMID:Conformation and proteolysis of glucagon and insulin in surfactant and lipid solutions. 328 14


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