Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of levamisole on muscle contraction and glycogen metabolism have been examined in isolated muscle-cuticle sections of the roundworm Ascaris suum. Muscle contraction occurred when various levels of levamisole were perfused through the preparation. At a levamisole concentration of 0.42 mM, the period of contraction lasted only about 6 min and was followed by a period of relaxation. During this relaxation period, there was an activation of glycogen synthase (EC 2.4.1.11), as evidenced by a decrease in the Ka values of glucose 6-phosphate for glycogen synthase to 0.26 mM from control values of 0.50 mM. The glycogen phosphorylase (EC 2.4.1.1) activity ratio decreased from 0.85 to 0.65, which indicated an inactivation of this enzyme. Concomitant with this activation of glycogen synthase and inactivation of phosphorylase there was an increased synthesis of glycogen. In addition, the presence of levamisole prevented both the serotonin-induced cyclic AMP accumulation and the activation of the cyclic AMP-dependent protein kinase (EC 2.7.1.37). However, levamisole did not significantly affect the changes in glycogen synthase and phosphorylase brought about by perfusion with the neurostimulator acetylcholine. Collectively, the data indicated that levamisole caused a transient muscle contraction followed by muscle relaxation, and the muscle relaxation effect appeared to be the result of a levamisole-inhibited cyclic AMP-mediated pathway of glycogen utilization.
Mol Pharmacol 1983 Mar
PMID:The role of cyclic AMP-mediated regulation of glycogen metabolism in levamisole-perfused Ascaris suum muscle. 630 Jun 47

Phosphoprotein phosphatase was purified from swine kidney by chromatography on DEAE-Sephadex A-50, Sephacryl S-200 and Sepharose 4B columns containing covalently bound hexanediamine and polylysine. The enzyme was purified more than 20000-fold and the homogeneous preparation had a specific activity of 2.8 micromol per min per mg of protein with saturating concentrations of 32P-histone as the substrate. The phosphatase showed only a single protein band when examined by polyacrylamide gel electrophoresis and a single protein peak containing all of the enzymatic activity was observed during chromatography on Sephadex G-100 column. The molecular weight of the purified enzyme was determined to be 70000 +/- 5000 by exclusion chromatography on a calibrated Sephadex G-100 column. Similar values were obtained by sucrose density centrifugation, 70000 +/- 5000, and polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate, 70000 +/- 3000. The purified enzyme catalyzed the dephosphorylation of the phosphorylated forms of glycogen synthase, phosphorylase, histone, phosphofructokinase, Type II regulatory subunit of cyclic AMP-dependent protein kinase, casein and protamine. The apparent Km values for these substrates were 3.6 microM, 2.8 microM, 66 microM, 3.3 microM, 8.0 microM, 6.6 microM and 100 microM, respectively. The enzyme did not hydrolyze low molecular weight phosphate esters such as glucose 6-phosphate, glycerol phosphate, adenosine nucleotides and inorganic pyrophosphate. The activity of the enzyme towards a phosphorylated protein substrate was competitively inhibited by the addition of other substrates. These results suggest that swine kidney contains a phosphoprotein phosphatase with a rather broad substrate specificity for a number of endogenous and exogenous phosphoprotein substrates.
Mol Cell Biochem 1983
PMID:Purification and properties of swine kidney phosphoprotein phosphatase. 630 89

Enhanced phosphorylase activation in hearts from hyperthyroid animals has been well documented. To elucidate the mechanisms responsible for the enhanced phosphorylase a formation, hearts from euthyroid and hyperthyroid rats were perfused by the Langendorff method with calcium (3.75 mM), isoproterenol, dibutryl cAMP and trifluoperazine, an inhibitor of calcium-calmodulin dependent enzymes. Comparative biochemical analyses revealed increased phosphorylase a formation in hearts from both euthyroid and hyperthyroid animals following exposure to calcium, dibutryl cAMP and isoproterenol. Hearts from hyperthyroid rats had an increased sensitivity to threshold concentrations of isoproterenol for both cAMP formation and phosphorylase b to a conversion. At higher concentrations of isoproterenol (10(-8) M and 3 x 10(-8) M), no significant differences in cAMP formation were noted between euthyroid and hyperthyroid animals in spite of persistently increased phosphorylase a levels in the hyperthyroid state. Trifluroperazine had no effect on basal phosphorylase a levels but significantly inhibited phosphorylase a formation in both groups following calcium or isoproterenol stimulation. However, enhanced phosphorylase a formation was still present in the hearts from hyperthyroid rats following trifluoperazine preperfusion. Determinations of phosphorylase kinase activity revealed a specific activity in the hyperthyroid animals twice that of the euthyroid controls. At least two mechanisms, an increased sensitivity to beta-adrenergic agents and increased cardiac phosphorylase kinase activity, may mediate the enhanced phosphorylase a formation found in hearts from hyperthyroid rats.
J Mol Cell Cardiol 1983 Mar
PMID:Mechanisms of enhanced phosphorylase activation in the hyperthyroid rat heart. 630 61

Synthase phosphatase, phosphorylase phosphatase and histone phosphatase activity in a leukocyte homogenate were found to have different sedimentation characteristics: both synthase phosphatase and phosphorylase phosphatase activity are associated with the microsomal fraction, while the majority of histone phosphatase activity (75-85%) was found in the cytosol. Synthase phosphatase, phosphorylase phosphatase and histone phosphatase activities accompanying the microsomal fraction are readily solubilized by 0.3% Triton X-100. When the solubilized microsomal enzymes were chromatographed on Sephadex G-200, the majority of synthase phosphatase, phosphorylase phosphatase and histone phosphatase activity migrated in single peaks corresponding to apparent molecular weights of 380 000, 250 000 and 68 000, respectively. A minor peak of 30 000, which had phosphatase activity against all three substrates was also obtained. Ethanol treatment resulted in solubilization and dissociation of the three phosphatase activities. It was found that although ethanol treatment resulted in a 4-fold increase of phosphorylase phosphatase activity, histone phosphatase activity was decreased (by 60%), while synthase phosphatase activity remained stable. Similar results were obtained when ethanol treatment was performed on the 17 000 X g supernatant. Chromatography of the ethanol-treated microsomes (or homogenate) on Sephadex G-200 showed that the phosphatase activity towards synthase D, phosphorylase a and phosphohistone coincided a Mr 30 000 species. Heat treatment of the Mr 30 000 peak resulted in dissociation of synthase phosphatase and phosphorylase phosphatase activity. Synthase phosphatase was inhibited by phosphorylase a in a kinetically non-competitive manner while histone phosphatase activity was not inhibited by synthase D (8.5 unit/ml) or by phosphorylase a (12 unit/ml).
Mol Cell Biochem 1984
PMID:Chromatographic characteristics and subcellular localization of synthase phosphatase, phosphorylase phosphatase and histone phosphatase in human polymorphonuclear leukocytes. 632 56

Organ cultures prepared from 18- to 19-day fetal and 3- to 6-day-old newborn rat liver were maintained for 2 days in Trowell's T8 medium without insulin and supplemented with 0.1% albumin and 300 mg% glucose. The atmosphere for culture was 95% O2 and 5% CO2. Medium alone was used for control cultures, whereas insulin, hydrocortisone, or insulin plus hydrocortisone were used in experimental groups. Explant glycogen stores were maintained better in cultures grown in hormone-supplemented media than in control cultures. Fetal explants were found to have higher levels of glycogen than controls in the insulin or insulin plus hydrocortisone groups. Postnatal explants did not have higher levels of glycogen in the hormone-treated groups. Gestational age appeared to determine whether the liver explants reacted to hydrocortisone or insulin to maintain glycogen stores. Enzymatic assays, in vitro of glycogen synthetase and phosphorylase, indicated that the fetal liver response to insulin plus hydrocortisone by increasing the total and independent form of glycogen synthetase; but similar enzyme studies on postnatal rat liver did not show convincing differences as to an effect on synthetase. No definite in vitro temporal relationships could be identified. Late in gestation, the effect of hydrocortisone on glycogen synthesis is apparently dependent on the presence of insulin. Insulin appears to be required for glycogen storage in vitro in the cultures of postnatal rat liver.
Exp Mol Pathol 1983 Apr
PMID:Comparative effects of insulin and hydrocortisone on glycogen content of fetal and newborn rat liver cultures. 640 78

The binding sites for the allosteric activator, AMP, to glycogen phosphorylase b are described in detail utilizing the more precise knowledge of the native structure obtained from crystallographic restrained least-squares refinement than has hitherto been available. Localized conformational changes are seen at the allosteric effector site that include shifts of between 1 and 2 A for residues Tyr75 and Arg309 and very small shifts for the region of residues 42 to 44 from the symmetry-related subunit. Kinetic studies demonstrate that NADH inhibits the AMP activation of glycogen phosphorylase b. Crystallographic binding studies at 3.5 A resolution show that NADH binds to the same sites on the enzyme as AMP, i.e. the allosteric effector site N, which is close to the subunit-subunit interface, and the nucleoside inhibitor site I, which is some 12 A from the catalytic site. The conformations of NADH at the two sites are different but both conformations are "folded" so that the nicotinamide ring is close (approx. 6 A) to the adenine ring. These conformations are compared with those suggested from solution studies and with the extended conformations observed in the single crystal structure of NAD+ and for NAD bound to dehydrogenases. Possible mechanisms for NADH inhibition of phosphorylase activation are discussed.
J Mol Biol 1983 Oct 25
PMID:Comparison of AMP and NADH binding to glycogen phosphorylase b. 641 89

Lithium ion, like insulin, activated adipocyte glycogen synthase with or without glucose in the medium. However, the effect of lithium ion was much greater than that of insulin under both conditions. The lithium-activated glycogen synthase was stable to both Sephadex chromatography and ethanol precipitation of the enzyme, indicating that the effect of lithium ion on glycogen synthase was through covalent modification of the enzyme. Glycogen synthase was significantly activated by lithium ion under conditions where concentrations of cellular ATP were unaffected. The effect of lithium ion on glycogen synthase was rapid and observed at concentrations as low as 1 to 3 mM, reaching a maximum at the concentration of 40 mM. It was thus the most sensitive of all the effects studied (see previous paper). Insulin further stimulated glycogen synthase at low concentrations but not at maximal concentration of lithium ion. Lithium-activated glycogen synthase was inhibited by both epinephrine and dibutyryl cyclic AMP, but was not affected by the removal of extracellular Ca++. Interestingly, lithium ion had no detectable effect on basal pyruvate dehydrogenase as well as on epinephrine-stimulated phosphorylase. The failure of lithium ion to thus mimic insulin actions on pyruvate dehydrogenase and on phosphorylase suggests that the action of lithium ion on glycogen synthase is quite specific and may be mediated by stimulating a phosphatase or by inhibiting a protein kinase acting specifically on glycogen synthase.
Mol Cell Biochem 1983
PMID:'Insulin-like' effects of lithium ion on isolated rat adipocytes. II. Specific activation of glycogen synthase. 641 71

Some enzymes of purine salvage were detected in the cell-free preparations from bloodstream forms of African trypanosomes: Trypanosoma vivax; T. brucei and T. congolense. Extracts of trypanosomes cleave adenosine and inosine hydrolytically except in T. congolense where adenosine cleavage was mediated by a phosphorylase. All the trypanosomes apparently lacked adenosine deaminase. Adenine aminohydrolase was found only in T. vivax while adenosine monophosphate deaminase was detected in T. brucei and T. congolense. There was no detectable adenosine kinase activity in T. brucei. A pathway is proposed for the metabolism of purines in these trypanosomes.
Mol Biochem Parasitol 1983 Dec
PMID:Comparative aspects of purine metabolism in some African trypanosomes. 641 98

Glycogen phosphorylase b (EC 2.4.1.1) has been purified from the muscle of the roundworm, Ascaris suum. The 223-fold purified enzyme was shown to be homogenous by high performance liquid chromatography (HPLC), gel filtration column chromatography and sodium dodecyl sulfate (SDS) gel electrophoresis. The apparent native molecular weight of the enzyme determined by size exclusion chromatography by HPLC and gel filtration corresponded to 200 000 and 199 000, respectively. The subunit molecular weight of the enzyme was determined to be 100 000 by electrophoresis in the presence of SDS. Therefore, the enzyme appears to be a dimer with identical or near identical subunits. The enzyme contained 1 mol of pyridoxal 5'-phosphate per mol subunit and exhibited an absorbance index E1% 280 of 13.8. The apparent isoelectric point of the enzyme is 5.53. The enzyme, inactive in the absence of AMP, can be converted to the active form by rabbit muscle phosphorylase kinase and MgATP. The molecular weight of the activated form of the enzyme is 200 000. Kinetic studies showed apparent Km values of 0.17% for glycogen, 36 mM for Pi and 52 mM for glucose-1-P. The apparent Ka for AMP was 0.22 mM.
Mol Biochem Parasitol 1983 Dec
PMID:Purification and characterization of phosphorylase B from Ascaris suum. 641 99

Maltose-negative mutations in the amylomaltase gene of Streptococcus pneumoniae were examined for the presence of nonsense mutations. Out of 28 single-site mutants tested, 3 were shown to be suppressible by an amber suppressor previously found by Gasc et al. (1979). In the presence of the suppressor these mutants manifested 10--30% of wild type amylomaltase activity. In addition to the amylomaltase governed by malM, and the maltosaccharide phosphorylase governed by malP (which maps to the side of malM distal to the regulatory gene, malR), a new maltose-inducible protein, governed by another gene, malX, was observed in gel electrophoretic patterns. The malX gene maps on the side of malM proximal to the malR gene. The approximate molecular weights of the amylomaltase, phosphorylase and malX polypeptides are 62,000, 87,000 and 50,000, respectively. There appear to be no polar effects of the nonsense mutations in the malM gene on synthesis of the gene products of either malP or malX. In a search for nonsense mutants at other loci, one was found in the end gene, which governs the major endonuclease, a membrane enzyme. None were detected among 5 mismatch-repair defective hex mutants analyzed.
Mol Gen Genet 1981
PMID:Nonsense mutations in the amylomaltase gene and other loci of Streptococcus pneumoniae. 646 Jan 54


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