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)

Gabonase, an enzyme which acts on fibrinogen and factor XIII in uniquely thrombin-like ways, was purified to electrophoretic homogeneity from the venom of Bitis gabonica. On sodium dodecyl sulfate-polyacrylamide electrophoresis, the reduced protein behaved as a single chain with Mr = 30,600. The enzyme contains 20.6% carbohydrate, no free sulfhydryl groups and hence, from amino acid analysis, five disulfide bonds. Its extinction coefficient (E1%1cm) at 280 nm is 9.6. Its pI is 5.3. Gabonase has an active serine residue, is inactivated by phenylmethanesulfonyl fluoride, and has an active histidine which reacts with the chloromethyl ketone of tosyl-L-lysine. Its NH2-terminal amino acid sequence (Val-Val-Gly-Gly-Ala-Glu-Cys-Lys-Ile-Asp-Gly-His-Arg-Cys-Leu-Ala-Leu-Leu -Tyr-) is homologous to the B chain of thrombin. The activity of the enzyme is stabilized by calcium ion. It exhibits strong N alpha-p-tosyl-L-arginine methyl esterase activity, hydrolyzes tripeptide nitroanilide derivatives weakly or not at all, and cleaves no peptide bonds in insulin, glucagon, or the S peptide of ribonuclease. Gabonase clots fibrinogen with a specific activity of 45 NIH thrombin-equivalent units/mg, releasing both fibrinopeptides A and B and showing substrate inhibition at fibrinogen concentrations of 3 mg/ml or greater. The enzyme also activates factor XIII. It is not inactivated by either heparin or hirudin.
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PMID:Thrombin-like enzyme from the venom of Bitis gabonica. Purification, properties, and coagulant actions. 352 80

To investigate dipeptide assimilation by the liver, a series of interrelated experiments were performed in rats. Partial hepatectomy prolonged the plasma half-life (min) of Gly-Ala (3.42 +/- 0.22 versus 4.90 +/- 0.35, p less than 0.05) but had no significant effect on plasma half-life of Gly-Leu, Gly-Pro, or Gly-Sar. We then investigated the rate of disappearance (mumol X (g liver X h)-1) of the above four dipeptides (initial concentration = 1 mM) from the medium during isolated liver perfusion. The order of dipeptide disappearance was: Gly-Leu (8.75 +/- 0.65) greater than Gly-Ala (3.36 +/- 0.46) greater than Gly-Pro (1.29 +/- 0.54) greater than Gly-Sar (0.35 +/- 0.12). This order of dipeptide disappearance corresponded exactly to the order of the rates of glycine accumulation in the medium during liver perfusion with the four dipeptides. Addition of glucagon had no effect on the disappearance rate of Gly-Ala from the medium, but reduced accumulation rates of glycine (3.39 +/- 0.30 versus 1.42 +/- 30, p less than 0.01) and alanine (4.42 +/- 0.66 versus 1.35 +/- 0.39, p less than 0.01). Finally, we found that hydrolysis by the liver plasma membranes and/or perfusion medium accounted for disappearance of dipeptides. In conclusion, the liver does not appear to have a transport system for dipeptides, but assimilates dipeptides by extracellular hydrolysis. Hydrolysis is achieved by enzymes either located on the plasma membranes or released from the cytosol. The amino acid residues released as the result of dipeptide hydrolysis are then taken up by the liver.
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PMID:Mechanism of hepatic assimilation of dipeptides. Transport versus hydrolysis. 353 28

The functions of the Trp-25 and Met-27 residues and the free carboxy terminus of glucagon have been debated for many years. Despite some semi-synthetic data to the contrary, comparison of the glucagon sequence with the other 5 members of this family of peptides, all of them amides and particularly growth hormone-releasing factor(1-29) amide and its recently described analogues, suggests that alterations to these positions should be quite well tolerated in terms of biological activity. To test this prediction, [Phe-25,Leu-27]-glucagon amide was synthesized in high yield and was found to actually have superior glycogenolytic activity (196%) to glucagon in the rat. Replacement of Gly-4 by D-Phe, which has been shown to give much enhanced glycogenolytic activity than glucagon itself, also increased the activity of [D-Phe-4,Phe-25,Leu-27]-glucagon amide (518%). The L-Phe-4-analogue, [Phe-4,25,Leu-27]-glucagon amide, in contrast, was 20 times less active (30%), strongly suggesting the presence of a beta-bend in this N-terminal region of glucagon. This was supported by Chou-Fasman structural predictions which indicate extensive folding in the 1-15 region. Indeed, additional conformational restriction by substitution of D-Ser in position 2 of glucagon also increased activity to 226%. [D-Gln-3]-glucagon was slightly less active (74%) than glucagon. Chou-Fasman calculations on glucagon were compared to similar treatments of the VIP, secretin, PHI, and GRF(1-29) sequences.
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PMID:Superactive amidated COOH-terminal glucagon analogues with no methionine or tryptophan. 374 51

The principal products derived from in vivo processing of anglerfish preproglucagon II were isolated and their structures determined. The structures were confirmed by a combination of automated Edman degradation, amino acid analysis, and fast atom bombardment mass spectrometry. The peptide corresponding to anglerfish preproglucagon II-(22-49) (numbering from the amino terminus of preproglucagon) was isolated intact and defines the site of signal cleavage to be between Gln-21 and Met-22. Glucagon from the anglerfish preproglucagon gene II was found to correspond to preproglucagon II-(52-80) (numbering from the amino terminus). Three forms of a glucagon-like peptide derived from preproglucagon II were also isolated. The structure of the longest form was consistent with the sequence of preproglucagon II-(89-122) deduced from the cDNA, His-Ala-Asp-Gly-Thr-Tyr-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Gln-Asp-Gln-Ala- Ala-Lys-Asp-Phe-Val-Ser-Trp-Leu-Lys-Ala-Gly-Arg-Gly-Arg-Arg-Glu. The carboxyl-terminal portion deduced from the cDNA remains intact in this form. A second form, preproglucagon II-(89-119) appears to result from proteolytic processing of the major form at the two adjacent arginine residues occurring at the carboxyl terminus. This second form has a glycine residue at its carboxyl terminus and is processed to the third form (preproglucagon II-(89-118)) which contains a carboxyl-terminal arginineamide. Radiolabeling studies in primary tissue culture support the observation that glucagon (preproglucagon II-(52-80], preproglucagon II-(89-122), and preproglucagon II-(89-119) are products of proglucagon processing in vivo.
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PMID:Isolation and structure of the principal products of preproglucagon processing, including an amidated glucagon-like peptide. 375 32

The relationships between changes in the plasma levels of immunoreactive insulin (IRI) and glucagon (IRG) in response to the postprandial increments of circulating amino acids were studied under normal physiological conditions in healthy dogs. In the presence of a unique postprandial physiological euglycemic "glucose clamp" which occurs in these dogs, plasma IRG rose to an earlier peak than IRI and both remained elevated for 16-19 hr. Amino acid (AA) profiles also showed postprandial incremental responses for up to 16 hr. Multiple correlation analyses indicated that only branched chain AAs were significantly correlated with IRI profiles and were devoid of a relationship to IRG. Similarly, only ornithine, lysine and glycine were significantly correlated with IRG profiles and devoid of a relationship to IRI. The significance of individual IRG stimulating effects of alanine and arginine were masked by other amino acid interactions, as significant intercorrelation was found among all 13 amino acids. Two equations were derived from the multiple regression analysis accounting for the postprandial time course of changes in IRI and IRG levels with only 5 amino acid concentrations: (1) (delta IRI) = 0.37 (delta Leu) -0.45(delta His), and (2) (delta IRG) = 0.55(delta Orn) + 0.37(delta Gly) -0.69 (delta Ser). These observations confirm the physiologic role in islet hormone secretion of the postprandial increments in circulating amino acids in the absence of glycemic change.
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PMID:Changes in blood amino acids account for the insulin and glucagon responses to mixed meals in dogs. 388 96

The work presented here aims at investigating the in vitro relationship between amino acids and pancreatic hormonal release in the suckling rat. Among the 20 most usual amino acids, 12 of them were tested on perifused pieces of pancreas in 5.5-day-old rats at a low glucose concentration. Their effects were compared to those induced by a 20 amino acid mixture. A 20 amino acid mixture (10.3 mM) stimulated glucagon and insulin release (154 and 208%, respectively). In the mixture, the 4 pooled amino acids Ala-Gly-Ser-Thr (at 1.4 instead of 4.2 mM) did not induce further modification of the glucagon or insulin release. However, the 3 branched chain amino acids Ile-Leu-Val (at 2.9 instead of 1.4 mM) or the following amino acids Arg-Asn-Phe-Pro-Tyr (at 3.2 instead of 1.6 mM) modulated glucagon or insulin release in the presence of the amino acid mixture. In the absence of Ile-Leu-Val, the amino acid mixture had no effect on the insulin release: 122 compared to 208%. This seems specific to the chemical nature of Ile-Leu-Val since in the absence of Arg-Asn-Phe-Pro-Tyr, the amino acid mixture was still effective on the insulin release (178 compared to 208%). In the absence of Ile-Leu-Val, the amino acid mixture was effective on glucagon release, and revealed the cellular specificity of the branched chain amino acid action.
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PMID:Chemical specificity of the effects of branched chain amino acids on glucagon and insulin release in the suckling rat. 389 29

Plasma membrane vesicles prepared from intact rat liver or isolated hepatocytes retain transport activity by systems A, ASC, N, and Gly. Selective substrates for these systems showed a Na+-dependent overshoot indicative of energy-dependent transport, in this instance, driven by an artificially-imposed Na+ gradient. Greater than 85% of Na+-dependent 2-aminoisobutyric acid (AIB) uptake was blocked by an excess of 2-(methylamino)isobutyric acid (MeAIB) with an apparent Ki of 0.6 mM. Intact hepatocytes obtained from glucagon-treated rats exhibited a stimulation of system A activity and plasma membrane vesicles isolated from those same cells partially retained the elevated activity. Transport activity induced by substrate starvation of cultured hepatocytes was also evident in membrane vesicles prepared from those cells. The membrane-bound glucagon-stimulated system A activity decays rapidly during incubation of vesicles at 4 degrees C (t1/2 = 13 h), but not at -75 degrees C. Several different inhibitors of proteolysis were ineffective in blocking the decay of transport activity. Hepatic system N transport activity was also elevated in plasma membrane vesicles from glucagon-treated rats, whereas system ASC was essentially unchanged. The results indicate that both glucagon and adaptive regulation cause an induction of amino acid transport through a plasma membrane-associated protein.
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PMID:Maintenance of glucagon-stimulated system A amino acid transport activity in rat liver plasma membrane vesicles. 396 88

Cathepsins M and B from rabbit liver lysosomes were separated by chromatography on Ultrogel AcA34 at low ionic strength and purified to homogeneity, and their catalytic and molecular properties were compared. Cathepsin M was relatively inactive with synthetic peptide substrates. Thus, it hydrolyzed benzoyl arginine naphthylamide at only one-fifth the rate observed with cathepsin B, and no activity was detected with Gly-Phe naphthylamide which is a relatively good substrate for cathepsin B. On the other hand, cathepsin M exhibited a preference for protein substrates. It was more active than cathepsin B in catalyzing the inactivation of the following enzymes: rabbit muscle or liver fructose-1,6-bisphosphate aldolases, rabbit liver fructose-1,6-bisphosphatase and pyruvate kinase, yeast glucose-6-phosphate dehydrogenase, and rabbit muscle glyceraldehyde-3-phosphate dehydrogenase. With glucagon as substrate, both enzymes showed similar peptidyl dipeptidase activities with some minor differences in peptide bond specificity. Cathepsins M and B are similar in size, with apparent molecular weights of 30,200 for cathepsin M and 28,800 for cathepsin B, and in amino acid composition and carbohydrate content. Each contains approximately 2-3 equivalents/mol glucosamine, 3 equivalents/mol mannose, and no fucose or galactosamine. They also show similar microheterogeneity in sodium dodecylsulfate-gel electrophoresis and isoelectric focusing; this microheterogeneity is probably related to differences in glycosylation. Extensive homology in primary structure for the two proteins was indicated by the similar patterns of peptides formed on digestion with trypsin.
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PMID:Purification and properties of rabbit liver cathepsin M and cathepsin B. 406 7

The administration of glucagon to rats causes a marked increase in the phosphorylation of a specific serine residue in lysine-rich (f1) histone of liver during a one-hour period following the administration of the hormone. It is proposed that histone phosphorylation is the mechanism by which glucagon, and perhaps other hormones whose actions are mediated by adenosine 3',5'-cyclic phosphate (cyclic AMP), induce RNA synthesis in target tissues. The incorporation of (32)P-phosphate into lysine-rich histone is determined by isolation of a tryptic peptide which contains the phosphorylated serine residue. This peptide is identical to the major tryptic phosphopeptide obtained from lysine-rich histone after phosphorylation in vitro by a purified cyclic AMP-dependent liver histone kinase preparation; the partial sequence Lys-Ala-SerPO(4)(Thr,Ser,Glu,Pro(2),Gly,Val,Ile,Leu)Lys has been determined for the peptide. Hydrocortisone and adrenocorticotrophic hormone do not cause a detectable increase in histone phosphorylation in liver. However, insulin, which like glucagon induces an actinomycin sensitive synthesis of liver enzymes, also causes increased histone phosphorylation.
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PMID:Phosphorylation of liver histone following the administration of glucagon and insulin. 431 47

Porcine ileal mucosa was homogenized and freeze-thawed in 0.05 M NH4HCO3 + 0.01 M EDTA + 1 mM benzamidine hydrochloride at pH 8.6. Subsequent stepwise precipitation with (NH4)2SO4 followed by fractionation on Sephadex G-50 medium and G-50 fine eluted with alkaline buffer and final fractionation on G-50 superfine in 1.0 M acetic acid yielded a pure protein of 13,000 daltons as determined by sodium dodecyl sulfate electrophoresis. The amino acid composition of the protein has been determined and it contains 126 residues with no tryptophan detectable. Tryptic peptide maps demonstrate that the protein does not contain glucagon and RIA of the peptide did not detect any immunoreactive glucagon or gastrin. The isoelectric point is 6.4. The intact protein is resistant to Edman degradation and the partial N-terminal sequences of two CNBr fragments are: Lys-Arg-Leu-Ala-Leu ...., Glu-Gly-Gly-Thr-Val-Val-Val-Asn-Ser.... The C-terminal residue, alanine was determined using carboxypeptidase Y. The isolated peptide, in the range of 10(-15)-10(-9) M stimulated oxyntic cell hydroxyl ion production in sections of guinea pig gastric fundus. The dose response was linear with biphasic peaks at 10(-14) and 10(-9) M and the maximal response to the peptide was equal to that observed with gastrin. The addition of either atropine (10(-5) M) or cimetidine (10(-5) M) with the peptide (10(-14) M) caused greater than 50% inhibition of oxyntic cell stimulation (P less than 0.005). This peptide is a potent stimulator of the oxyntic cell and its effect is inhibited by muscarinic cholinergic and H2 receptor blockers. Hence, it represents a significant component of the physiological enterooxyntin effect observed in response to intestinal meals.
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PMID:Isolation and partial characterization of an entero-oxyntin from porcine ileum. 609 Jan 3


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