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At least 289 records · Page 16Linked to original sources
PubMed1999

The degradation of glycogen in the lysosomes of newborn rat hepatocytes: glycogen-, maltose- and isomaltose-hydrolyzing acid alpha glucosidase activities in liver.

The lysosomal glucosidase activities and glycogen degradation in newborn rat liver were studied by using biochemical assays, electron microscopy and quantitative morphometry. Glycogen-hydrolyzing, maltose-hydrolyzing and isomaltose-hydrolyzing activities were low at birth but increased afterwards. At the age of 6 hours they were markedly elevated. Actinomycin prevented the development of glucosidase activities indicating that these depend on protein synthesis. Parenteral glucose inhibited all three activities. This was apparently due to the abolition of normal postnatal hypoglycemia and the need for blood glucose. Cyclic AMP increased the glycogen-hydrolyzing but not the maltose-hydrolyzing activity. Propranolol inhibited the glycogen-hydrolyzing but not the maltose-hydrolyzing activity. The observations of this study provide further support for the hypothesis made by previous investigators that these activities are due to different enzymes.

Animals↗
PubMed1995

A case of glycogen storage disease type III (glycogen debranching enzyme deficiency) with liver cirrhosis and hypertrophic cardiomyopathy.

We present a 26-year-old woman with glycogen storage disease type III (debranching enzyme deficiency) complicated with liver cirrhosis and hypertrophic cardiomyopathy. Glycogen debranching enzyme has two catalytic sites, oligo-1,4,-1,4- glucantransferase (EC 2.4.1.25) and amylo-1,6-glucosidase (EC 3.2.1.33). Variability in the clinical phenotype could be a function of the involvement of one or other catalytic site, or differences in tissue expression of the defective enzyme, or both. We hypothesize that some subtypes of glycogen storage disease (GSD) type III may cause liver cirrhosis as seen in GSD type IV due to the accumulation of glycogen of abnormal structure.

Adult↗
PubMed2003

Evaluation of glycogen loss in human liver transplants. Histochemical zonation of glycogen loss in cold ischemia and reperfusion.

To find a prognosis model of human liver transplant, we evaluate 62 surgical biopsies for the loss of glycogen and its variations in relation to cold ischemia, reperfusion, lobular zonation and donor's ages. We applied univariate, multivariate and discriminant analysis and logistic regression. There was a clear lobular zonation of glycogen during cold ischemia and at reperfusion. During cold ischemia, the mean loss was 48% in periportal zones and 74% in pericentrilobular zones. At reperfusion, it was in the range of 60% in periportal zones and 95% in pericentrilobular zones. It was observed in 64% of the grafts for an ischemia time less than 10 hr and in 82% of the grafts for an ischemia time of 10 hr or more. It was increased by 90% at reperfusion with pericentral predominance. Donors' age was an aggravating factor of glycogen loss beyond 28 years of age. In conclusion, in periportal zones, mean global glycogen depletion was about 54% during cold ischemia and reperfusion. It decreased by 90% at reperfusion with pericentral predominance. Logistic regression has allowed modelization of cold ischemia and reperfusion.

Adolescent↗
PubMed1992

Coordinate regulation of glycogen metabolism in the yeast Saccharomyces cerevisiae. Induction of glycogen branching enzyme.

The yeast glycogen branching enzyme (EC 2.4.1.18) is shown to be induced in batch culture simultaneously with the onset of intracellular glycogen accumulation. The branching enzyme structural gene (GLC3) has been cloned. Its predicted amino acid sequence is very similar to procaryotic branching enzymes. Northern analysis indicates that GLC3 mRNA abundance increases in late exponential growth phase coincident with glycogen accumulation. Disruption of the branching enzyme structural gene establishes that branching enzyme activity is an absolute requirement for maximal glycogen synthesis.

1,4-alpha-Glucan Branching Enzyme↗
PubMed1979

Contribution of cyclic adenosine 3':5'-monophosphate to the regulation of bacterial glycogen synthesis in vivo. Effect of carbon source and cyclic adenosine 3':5'-monophosphate on the quantitative relationship between the rate of glycogen synthesis and the cellular concentrations of glucose 6-phosphate and fructose 1,6-diphosphate in Escherichia coli.

When either fructose, glycerol, or succinate served as a sole source of carbon and energy in nitrogen-starved cultures of Escherichia coli W4597(K) the values of the kinetic constants of the equation that expresses the relationship between glycogen synthesis and hexose phosphates were different from the values observed when glucose was the sole source of carbon and energy. Addition of glucose during either exponential growth or nitrogen starvation to a culture using one of the other carbon sources slowed the rate of glycogen synthesis and shifted the values of the constants toward the values observed in cultures using glucose alone. Addition of cyclic AMP (cyclic adenosine 3':5'-monophosphate) during exponential growth of a culture using glucose caused the values of the constants to be shifted toward the values observed in cultures using a carbon source other than glucose. In all of the metabolic conditions studied in this report the adenylate energy charge ((ATP + 1/2 ADP)/(ATP + ADP + AMP)) and the level of the rate-limiting enzyme of glycogen synthesis, ADP-glucose synthetase (glucose 1-phosphate adenylyltransferase, EC 2.7.7.27), were the same. The data presented here indicate that the difference we observed in the quantitative relationship for glycogen synthesis is the result of the different cellular levels of cyclic AMP in the cells using glucose and the cells using one of the other carbon sources. Since cyclic AMP does not affect the velocity of ADP-glucose synthetase in vitro, apparently a change in the cellular level of cyclic AMP causes a shift in the cellular level of a presently unknown (and previously undetected) effector of this enzyme. The shift in the level of this effector evidently alters the response of the enzyme in vivo to the substrate glucose 1-phosphate and the activator fructose 1,6-diphosphate.

Adenine Nucleotides↗
PubMed1986

Phosphorylation of rabbit muscle glycogen synthase by casein/glycogen synthase kinase-1 (CK-1). Stoichiometry and distribution of the phosphorylation sites on the glycogen synthase subunit.

The stoichiometry of the phosphorylation of rabbit muscle glycogen synthase by casein/glycogen synthase kinase-1 (CK-1) depended on the concentration of protein kinase in the assay and reached values of 7-8 mol/mol subunit at high concentrations. Phosphorylation by CK-1 above 4 mol/mol subunit promoted a further decrease of glycogen synthase activity when determined by the low glucose-6-phosphate/high glucose-6-phosphate activity ratio assay. Analysis by limited proteolysis with trypsin and chymotrypsin showed that all of the regions in glycogen synthase phosphorylated by casein/glycogen synthase kinase-2 (CK-2), the catalytic subunit of cyclic AMP-dependent protein kinase (A-kinase), FA/glycogen synthase kinase-3 (FA/GSK-3) and phosphorylase b kinase were also phosphorylated by CK-1. Digestion with CNBr of glycogen synthase phosphorylated by CK-1 revealed the presence of the two phosphopeptides also labeled by the other protein kinases, the largest phosphopeptide (CB2) containing more phosphorylation sites for CK-1 than the smallest one (CB1). Three phosphopeptides (CB2-c, CB2-d and CB2-e) were obtained by trypsinization of CB2 phosphorylated by CK-1. None of them coincided with those labeled by A-kinase, a fact that was confirmed by the additivity of the effect of both protein kinases. In contrast, CB2-d comigrated with the peptide phosphorylated by FA/GSK-3, and CB2-e with that labeled by CK-2, whereas CB2-c would correspond to a new phosphopeptide.

Animals↗
PubMed1977

[Conditions for glycogen retention in smears of isolated cells. I. Cytofluorimetric analysis of glycogen content in cells obtained by different methods of isolation].

A cytofluorimetrical study was made of glycogen content on smears of isolated rat liver cells, obtained by perfusion of different solutions: 1/15 M phosphate buffer, the Locke solution, only the Locke solution plus sodium citrate, a calcium-free Locke solution, 0.25 M sucrose, physiological saline, Versene. No loss of glycogen occurred during any perfusion procedure, however, it took place during the smear preparation. The main cell injury is observed due to mechanical factors. An additional treatment of liver, after perfusion, by homogenization and centrigugation at mild conditions decreases the cell glycogen content by 30%. The least cell injury and the best glycogen retention was achieved when phosphate buffers were employed for cell isolation.

Animals↗
PubMed1989

Multisite phosphorylation of the glycogen-binding subunit of protein phosphatase-1G by cyclic AMP-dependent protein kinase and glycogen synthase kinase-3.

The glycogen-binding (G) subunit of protein phosphatase-1G is phosphorylated stoichiometrically by glycogen synthase kinase-3 (GSK3), and with a greater catalytic efficiency than glycogen synthase, but only after prior phosphorylation by cyclic AMP-dependent protein kinase (A-kinase) at site 1. The residues phosphorylated are the first two serines in the sequence AIFKPGFSPQPSRRGS-, while the C-terminal serine (site 1) is one of the two residues phosphorylated by A-kinase. These findings demonstrate that (i) the G subunit undergoes multisite phosphorylation in vitro; (ii) phosphorylation by GSK3 requires the presence of a C-terminal phosphoserine residue; (iii) GSK3 can synergise with protein kinases other than casein kinase-2.

Amino Acid Sequence↗
PubMed1999

Glycogen storage disease type IIIa: first report of a causative missense mutation (G1448R) of the glycogen debranching enzyme gene found in a homozygous patient.

Several different mutations in the glycogen-debranching enzyme gene AGL have been found in patients with glycogen storage disease type III (GSD III) to date, but no missense mutations have been reported for GSD III, only nonsense, splicing, and deletion/insertion lesions. Here we describe a novel G1448R missense mutation in a Japanese GSD IIIa patient from a consanguineous family. Sequence analysis of cDNA from the patient' liver specimen revealed two separate nucleotide changes: a G-to-A transition at nucleotide 3737 in exon 26 (3737G>A) and a G-to-C transversion at nucleotide 4742 in exon 33 (4742G>C), both of which result in substitution of glycine by arginine (G1115R and G1448R). Because homo-zygotes for G1115R were found in healthy controls, G1115R seems to be a polymorphism. Restriction fragment length polymorphism analysis with Bsa JI showed that the patient was homozygous for G1448R and that none of the normal controls had the mutation. This missense mutation is located at a putative glycogen-binding site that is indispensable for enzyme activity. Thus, G1448R is likely to be the causative mutation in this patient. This is the first report of a missense mutation associated with GSD III.

Amino Acid Substitution↗
PubMed2002

Guidelines for management of glycogen storage disease type I - European Study on Glycogen Storage Disease Type I (ESGSD I).

UNLABELLED: Life-expectancy in glycogen storage disease type I (GSD I) has improved considerably. Its relative rarity implies that no metabolic centre has experience of large series of patients and experience with long-term management and follow-up at each centre is limited. There is wide variation in methods of dietary and pharmacological treatment. Based on the data of the European Study on Glycogen Storage Disease Type I, discussions within this study group, discussions with the participants of the international SHS-symposium 'Glycogen Storage Disease Type I and II: Recent Developments, Management and Outcome' (Fulda, Germany; 22-25th November 2000) and on data from the literature, guidelines are presented concerning: (1). diagnosis, prenatal diagnosis and carrier detection; (2). (biomedical) targets; (3). recommendations for dietary treatment; (4). recommendations for pharmacological treatment; (5). metabolic derangement/intercurrent infections/emergency treatment/preparation elective surgery; and (6). management of complications (directly) related to metabolic disturbances and complications which may develop with ageing and their follow-up. CONCLUSION: In this paper guidelines for the management of GSD I are presented.

Glycogen Storage Disease Type I↗
PubMed1998

A novel point mutation in an acceptor splice site of intron 32 (IVS32 A-12-->G) but no exon 3 mutations in the glycogen debranching enzyme gene in a homozygous patient with glycogen storage disease type IIIb.

Genetic deficiency of the glycogen-debranching enzyme (debrancher) causes glycogen storage disease type III (GSD III), which is divided into two subtypes: IIIa and IIIb. In GSD IIIb, glycogen accumulates only in the liver, whereas both liver and muscles are involved in GSD IIIa. The molecular basis for the differences between the two subtypes has not been fully elucidated. Recently, mutations in exon 3 of the debrancher gene were reported to be specifically associated with GSD IIIb. However, we describe a homozygous GSD IIIb patient without mutations in exon 3. Analysis of the patient's debrancher cDNA revealed an 11-bp insertion in the normal sequence. An A to G transition at position -12 upstream of the 3' splice site of intron 32 (IVS 32 A-12-->G) was identified in the patient's debrancher gene. No mutations were found in exon 3. Mutational analysis of the family showed the patient to be homozygous for this novel mutation as well as three polymorphic markers. Furthermore, the mother was heterozygous and the parents were first cousins. The acceptor splice site mutation created a new 3' splice site and resulted in insertion of an 11-bp intron sequence between exon 32 and exon 33 in the patient's debrancher mRNA. The predicted mutant enzyme was truncated by 112 amino acids as a result of premature termination. These findings suggested that a novel IVS 32 A-12-->G mutation caused GSD IIIb in this patient.

Adolescent↗
PubMed1978

Structure of the polysaccharide formed by incubating glycogen with D-[14C]glucose in the presence of the glycogen debranching enzyme [amylo-(1 linked to 6)-glucosidase-4-alpha-glucanotransferase].

[14C]Glycogen has been synthetized in vitro by incubating D-[14C]glucose with rabbit-liver glycogen in the presence of a pure preparation of the glycogen debranching enzyme [amylo-(1 linked to 6)-glucosidase-4-alpha-glucanotransferase]. The course of the reaction has been monitored and 14C-products isolated after 30 min and 5 h. The distribution of D-[14C]glucose groups in the polysaccharides has been determined by debranching the molecules with a crystalline isoamylase from Pseudomonas. The quantities of unlabeled and 14C-linear unit chains containing D-[14C]glucose at their reducing ends have been determined by paper chromatography followed by enzymic degradation and analysis. In the 30-min product, between 65 and 85% of the D-[14C]glucose groups were covered by unlabeled groups because of transferase action. In the 5-h product, the extent of covering approached 100%. Extensive redistribution of unlabeled groups also was found to have occurred, even in the early stages of the reaction. It is concluded that the D-[14C]glucose incorporation assay for amylo-(1 linked to 6)-glucosidase, as ordinarily carried out, is probably not specific just for the hydrolytic action of this enzyme, but that it depends indirectly on its transferase activity as well.

Animals↗
PubMed2000

Time-co-ordinated control of glycogen synthase, protein phosphatase 2A and protein kinase CK2 during culture growth in Yarrowia lipolytica in relation to glycogen metabolism.

In the growth course of the lipolytic yeast Yarrowia lipolytica, the activities of protein phosphatase 2A (PP2A) and glycogen synthase (GS) rise during the exponential phase and concomitantly glycogen storage occurs in the cells. There is also an increase in the independence ratio (RI) indicating a shift from an inactive phosphorylated GS form to an active dephosphorylated GS form. During the early stationary phase, an increase in protein kinase CK2 (CK2) activity, a reversion of RI variation and a glycogen content decrease are observed. GS activity proved to be a good indicator of early culture growth phase. Experiments carried out with enzymes purified from Y. lipolytica show strong RI variations upon the action of CK2 and PP2Ac, and 32P incorporation into GS protein through phosphorylation by CK2. GS activity would be controlled by the sequential action of PP2A and CK2.

Casein Kinase II↗
PubMed2003

A novel mutation (G233D) in the glycogen phosphorylase gene in a patient with hepatic glycogen storage disease and residual enzyme activity.

We identified a novel mutation in the glycogen phosphorylase gene (PGYL) in a Chinese patient with glycogen storage disease (GSD) type VI. The patient presented with gross hepatomegaly since the age of two without history of any hypoglycemic attack. Otherwise, he was largely asymptomatic. Liver tissue enzyme assays revealed a mild deficiency of total glycogen phosphorylase. Both PGYL and PHKA2 genes were sequenced. The patient was homozygous of a missense mutation G233D in PGYL. This location forms a hairpin turn secondary structure and the small glycine residue is completely conserved in all the orthologous proteins from Escherichia coli to mammals. This is the sixth reported mutation of this form of GSD.

Amino Acid Sequence↗
PubMed1975

Enzymes regulating glycogen metabolism in swine subcutaneous adipose tissue. II. Glycogen synthase.

Glycogen synthase from swine adipose tissue was purified to apparent homogeneity using ethanol precipitation, DEAE chromatography, and affinity chromatography utilizing glucosamine 6-phosphate as the ligand. The purified enzyme migrated as a single protein component during electrophoresis on polyacrylamide gels at pH 7.3 although some protein failed to enter the running gel. Enzyme incubated with sodium dodecyl sulfate (SDS) migrated as one component (mol wt similar to 90,000) on SDS-polyacrylamide gel electrophoresis. The enzyme was relatively unstable at all stages of the purification procedure, but stability was increased in the presence of glucose 6-phosphate, UDPG, or glycerol. The isoelectric point of the purified enzyme and of enzyme activity in crude homogenates was pH 4.8. The sedimentation coefficient of the enzyme in crude homogenates was 8.5 S. The pH-activity profile showed an optimum at pH 7.8 in the absence of glucose 6-phosphate but no definable optimum between pH 7.0 and 9.2 in its presence. The Km of glycogen synthase I for UDPG was 250 muM in the absence and 37 muM in the presence of glucose 6-phosphate; the K-a for glucose 6-phosphate was 18 mu-M. The K-m of glycogen synthase D for UDPG was 130 mu-M in the presence of glucose 6-phosphate; the Ka for glucose 6-phosphate was 1 mM. The anions sulfate and phosphate activated the enzyme when assays were performed in the absence of glucose 6-phosphate. Fluoride produced activation of enzyme assayed either in the presence or in the absence of glucose 6-phosphate.

Adipose Tissue↗
PubMed1995

Effects of C-1-substituted glucose analogue on the activation states of glycogen synthase and glycogen phosphorylase in rat hepatocytes.

A series of glucose-analogue inhibitors of glycogen phosphorylase b (GPb) has been designed, synthesized and investigated in crystallographic binding and kinetic studies. The aim is to produce a compound that may exert more effective control over glycogen metabolism than the parent glucose molecule and which could alleviate hyperglycaemia in Type-II diabetes. N-Acetyl-beta-D-glucopyranosylamine (1-GlcNAc) has a Ki for muscle GPb in crude extracts of 30 microM, 367-fold lower than that of beta-D-glucose [Board, Hadwen and Johnson (1995) Eur. J. Biochem. 228, 753-761]. In the current work, the effects of 1-GlcNAc on the activation states of GP and glycogen synthase (GS) in cell-free preparations and in isolated hepatocytes are reported. In gel-filtered extracts of liver, which lack ATP for kinase activity, 1-GlcNAc produced a rapid and time-dependent inactivation of GP with a subsequent activation of GS. Effects of 1-GlcNAc on both enzymes were stronger than those of glucose, with 0.8 mM 1-GlcNAc being equipotent with 50 mM glucose. At 1 mM, 1-GlcNAc enhanced the dephosphorylation of exogenous GPa by liver extracts (600%) and by muscle extracts (75%). This represents an approximately 500-fold improvement on glucose for the liver activity and 40-fold for the muscle activity. In whole hepatocytes, 1-GlcNAc showed an approximately 5-fold enhancement of glucose effects for GP inactivation but failed to elicit activation of GS. Glucose-induced activation of GS in whole hepatocytes was reversed by subsequent addition of 1-GlcNAc. However, when GS activation was achieved via the adenosine analogue and kinase inhibitor, 5'-iodotubercidin (ITU), subsequent addition of 1-GlcNAc allowed continued activation of GS. Phosphorylation of 1-GlcNAc in rat hepatocytes was established using radiolabelled material. The rate of phosphorylation was 1.60 nmol/min per 10(6) cells at 20 mM 1-GlcNAc but was reduced by the presence of 50 microM ITU (0.775 nmol/min per 10(6) cells). It is suggested that the phosphorylated derivative of 1-GlcNAc formed in hepatocytes is 1-GlcNAc 6-phosphate and that the presence of this species is responsible for the failure of 1-GlcNAc to activate GS. The relative importance of the reduction in concentration of GPa versus increased glucose 6-phosphate levels for activation of GS is discussed.

Acetylglucosamine↗
PubMed2003

Use of lithium and SB-415286 to explore the role of glycogen synthase kinase-3 in the regulation of glucose transport and glycogen synthase.

Glycogen synthase kinase 3 (GSK3) is inactivated by insulin and lithium and, like insulin, Li also activates glycogen synthase (GS) via inhibition of GSK3. Li also mimics insulin's ability to stimulate glucose transport (GT), an observation that has led to the suggestion that GSK3 may coordinate hormonal increases in GT and glycogen synthesis. Here we have used Li and SB-415286, a selective GSK3 inhibitor, to establish the importance of GSK3 in the hormonal activation of GT in terms of its effect on GS in L6 myotubes and 3T3-L1 adipocytes. Insulin, Li and SB-415286 all induced a significant inhibition of GSK3, which was associated with a marked dephosphorylation and activation of GS. In L6 myotubes, SB-415286 induced a much greater activation of GS (6.8-fold) compared to that elicited by insulin (4.2-fold) or Li (4-fold). In adipocytes, insulin, Li and SB-415286 all caused a comparable activation of GS despite a substantial differentiation-linked reduction in GSK3 expression ( approximately 85%) indicating that GSK3 remains an important determinant of GS activation in fat cells. Whilst Li and SB-415286 both inhibit GSK3 in muscle and fat cells, only Li stimulated GT. This increase in GT was not sensitive to inhibitors of PI3-kinase, MAP kinase or mTOR, but was suppressed by the p38 MAP kinase inhibitor, SB-203580. Consistent with this, phosphorylation of p38 MAP kinase induced by Li correlated with its stimulatory effect on GT. Our findings support a crucial role for GSK3 in the regulation of GS, but based on the differential effects of Li and SB-415286, it is unlikely that acute inhibition of GSK3 contributes towards the rapid stimulation of GT by insulin in muscle and fat cells.

3T3 Cells↗
PubMed2003

De novo synthesis of bacterial glycogen: Agrobacterium tumefaciens glycogen synthase is involved in glucan initiation and elongation.

Evidence is presented indicating that initiation of glycogen synthesis in Agrobacterium tumefaciens does not require the presence of alpha(1,4)-linked glucans. Crude cell extracts incubated with ADP-glucose (Glc) were able to form alpha(1,4)-linked glucans despite the fact that cells used for extract preparation displayed a genotype that prevented synthesis of Glc-containing sugar nucleotides and thus preformation of alpha(1,4)-linked glucans and that the defined growth medium used contained glycerol as carbon source. A. tumefaciens glycogen synthase (GS) purified to homogeneity from the above-mentioned cells was able to build its own primer by transferring Glc residues from ADP-Glc to an amino acid(s) in the same protein. Primed GS then became the substrate for further GS-catalyzed glucan elongation. It was concluded that, contrary to what happens in mammalian and yeast cells in which two different proteins are required for linear alpha(1,4)-linked glucan formation (glycogenin for initiation and GS for further elongation), in A. tumefaciens and probably in all other bacteria, the same protein is involved in both glycogen initiation and elongation.

Agrobacterium tumefaciens↗