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Information on EC 2.4.1.1 - glycogen phosphorylase and Organism(s) Rattus norvegicus and UniProt Accession P09811
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2.4.1.1 glycogen phosphorylaseIUBMB Comments
This entry covers several enzymes from different sources that act in vivo on different forms of (1->4)-alpha-D-glucans. Some of these enzymes catalyse the first step in the degradation of large branched glycan polymers - the phosphorolytic cleavage of alpha-1,4-glucosidic bonds from the non-reducing ends of linear poly(1->4)-alpha-D-glucosyl chains within the polymers. The enzyme stops when it reaches the fourth residue away from an alpha-1,6 branching point, leaving a highly branched core known as a limit dextrin. The accepted name of the enzyme should be modified for each specific instance by substituting "glycogen" with the name of the natural substrate, e.g. maltodextrin phosphorylase, starch phosphorylase, etc.
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Word Map
- 2.4.1.1
- amp
-
glycogenolysis
- hepatocytes
- mcardle
- glucagon
- glucose-6-phosphatase
- pyridoxal
- hexokinase
- 6-phosphate
- creatine
- epinephrine
- myopathy
- phosphorylases
-
phosphofructokinase
- intolerance
-
gluconeogenesis
- glucose-1-phosphate
-
phosphorolysis
- bb
- troponins
-
antidiabetic
- sarcoplasm
- maltodextrins
-
amp-dependent
- isoproterenol
- vasopressin
-
gluconeogenic
- phenylephrine
- glucokinase
- rhabdomyolysis
- myoglobinuria
- pp1
-
beta-adrenergic
- adrenaline
- phosphatase-1
- phosphocreatine
- phosphoglucomutase
-
debranching
- soleus
-
glucose-6-p
- adp-glucose
- g6pase
-
glucagon-stimulated
- inhibitor-2
-
2,6-bisphosphate
-
glycogenesis
-
t-state
- amylose
- biotechnology
- amyloplasts
- medicine
-
heart-type
- agriculture
- analysis
- synthesis
- drug development
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
glycogen phosphorylase, phosphorylase a, phosphorylase b, myophosphorylase, muscle phosphorylase, glycogen phosphorylase b, glycogen phosphorylase a, muscle glycogen phosphorylase, starch phosphorylase, maltodextrin phosphorylase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
1,4-alpha-glucan phosphorylase
-
-
-
-
alpha-glucan phosphorylase
-
-
-
-
amylopectin phosphorylase
-
-
-
-
amylophosphorylase
-
-
-
-
glucan phosphorylase
-
-
-
-
glucosan phosphorylase
-
-
-
-
glycogen phosphorylase
granulose phosphorylase
-
-
-
-
maltodextrin phosphorylase
-
-
-
-
muscle phosphorylase
-
-
-
-
muscle phosphorylase a and b
-
-
-
-
myophosphorylase
-
-
-
-
phosphorylase a
phosphorylase, alpha-glucan
-
-
-
-
polyphosphorylase
-
-
-
-
potato phosphorylase
-
-
-
-
starch phosphorylase
-
-
-
-
glycogen phosphorylase
-
-
-
-
phosphorylase a
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hexosyl group transfer
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(1->4)-alpha-D-glucan:phosphate alpha-D-glucosyltransferase
This entry covers several enzymes from different sources that act in vivo on different forms of (1->4)-alpha-D-glucans. Some of these enzymes catalyse the first step in the degradation of large branched glycan polymers - the phosphorolytic cleavage of alpha-1,4-glucosidic bonds from the non-reducing ends of linear poly(1->4)-alpha-D-glucosyl chains within the polymers. The enzyme stops when it reaches the fourth residue away from an alpha-1,6 branching point, leaving a highly branched core known as a limit dextrin. The accepted name of the enzyme should be modified for each specific instance by substituting "glycogen" with the name of the natural substrate, e.g. maltodextrin phosphorylase, starch phosphorylase, etc.
CAS REGISTRY NUMBER
COMMENTARY
9035-74-9
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(1,4-alpha-D-glucosyl)n + phosphate
(1,4-alpha-D-glucosyl)n-1 + alpha-D-glucose 1-phosphate
-
polysaccharide substrate is glycogen
-
-
?
[(1->4)-alpha-D-glucosyl]n + phosphate
[(1->4)-alpha-D-glucosyl]n-1 + alpha-D-glucose 1-phosphate
[(1->4)-alpha-D-glucosyl]n + phosphate
[(1->4)-alpha-D-glucosyl]n-1 + alpha-D-glucose 1-phosphate
-
-
-
r
[(1->4)-alpha-D-glucosyl]n + phosphate
[(1->4)-alpha-D-glucosyl]n-1 + alpha-D-glucose 1-phosphate
-
-
-
r
[(1->4)-alpha-D-glucosyl]n + phosphate
[(1->4)-alpha-D-glucosyl]n-1 + alpha-D-glucose 1-phosphate
-
glycogen metabolism
-
?
additional information
?
-
-
increased enzyme activity increases 5-phosphoribosyl-1-diphosphate availability in hepatocyte cultures and vice versa, glycogenolysis is a major contributor to PRPP generation in liver tissue in the basal state
-
-
?
additional information
?
-
-
the enzyme regulates the association of glycogen synthase with a proteoglycogen substrate in hepatocytes
-
-
?
additional information
?
-
-
glycogen phosphorylase is dynamically regulated during and after status in the adult rat, and may have an important role in the pilocarpine model of epilepsy
-
-
?
additional information
?
-
glycogen phosphorylase activity is measured in the direction of glycogen degradation (phosphorolysis)
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(1,4-alpha-D-glucosyl)n + phosphate
(1,4-alpha-D-glucosyl)n-1 + alpha-D-glucose 1-phosphate
-
polysaccharide substrate is glycogen
-
-
?
[(1->4)-alpha-D-glucosyl]n + phosphate
[(1->4)-alpha-D-glucosyl]n-1 + alpha-D-glucose 1-phosphate
[(1->4)-alpha-D-glucosyl]n + phosphate
[(1->4)-alpha-D-glucosyl]n-1 + alpha-D-glucose 1-phosphate
-
-
-
r
[(1->4)-alpha-D-glucosyl]n + phosphate
[(1->4)-alpha-D-glucosyl]n-1 + alpha-D-glucose 1-phosphate
-
glycogen metabolism
-
?
additional information
?
-
-
increased enzyme activity increases 5-phosphoribosyl-1-diphosphate availability in hepatocyte cultures and vice versa, glycogenolysis is a major contributor to PRPP generation in liver tissue in the basal state
-
-
?
additional information
?
-
-
the enzyme regulates the association of glycogen synthase with a proteoglycogen substrate in hepatocytes
-
-
?
additional information
?
-
-
glycogen phosphorylase is dynamically regulated during and after status in the adult rat, and may have an important role in the pilocarpine model of epilepsy
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-methyl-3-([4-(2-thienylmethyl)phenyl]amino)quinoxalin-2(1H)-one
-
50% inhibition at 0.00011 mM in glycogenolysis assay, no bioavailability in vivo
1-[(2S)-2-([(5-chloro-1H-indol-2-yl)carbonyl]amino)-3-phenylpropanoyl]azetidine-3-carboxylic acid
-
i.e. CP-403700, indole-site inhibitor, suppression of hepatic glycogenolysis
3-[(4-isoxazolidin-3-ylphenyl)amino]-1-methylquinoxalin-2(1H)-one
-
50% inhibition at 0.00011 mM in glycogenolysis assay, no bioavailability in vivo
4-[(4-methyl-3-oxo-3,4-dihydroquinoxalin-2-yl)amino]-N-(2-thienylmethyl)benzamide
-
50% inhibition at 0.00014 mM in glycogenolysis assay, no bioavailability in vivo
Caffeine
-
5 mM, 95% inhibition of heart phosphorylase Ib in the presence of 1 mM AMP, 30% inhibition of heart phosphorylase IIb
additional information
structure-based inhibitor design targeting glycogen phosphorylase b, virtual screening, synthesis, biochemical and biological assessment of N-acyl-beta-D-glucopyranosylamines, overview. Determination of the effects of the enzyme inhibitors on conversion of glycogen phosphorylase a to b
-
additional information
slight inhibition by azobenzene glucosides. After irradiation and subsequent conversion to the (Z)-form, the inhibitory potency of the azobenzene glucoside does not significantly change for the rat muscle enzyme form. The anomeric ratio of alpha:beta form is approximately 1:4
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
protein kinase A
-
activates the enzyme via phosphorylation, which is induced by dibutyryl cAMP, forskolin, and glucagon
-
additional information
-
Arg-vasopressin and phenylephrine activate the enzyme through the phosphoinositide cascade
-
5'-AMP
-
half-maximal activation of phosphorylase Ib at 0.022 mM, 0.007 mM for phosphorylase IIb
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.6
4-((E)-azobenzene)-beta-D-glucoside
Rattus norvegicus
untreated enzyme, pH 7.0, 30°C
0.032
4-((Z)-azobenzene)-beta-D-glucoside
Rattus norvegicus
enzyme after irradiation and subsequent conversion to the (Z)-form, pH 7.0, 30°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
at the protein level, but not at the mRNA level, the content of brain isoform of glycogen phosphorylase is similar in heart and brain. Muscle isoform of glycogen phosphorylase is more abundant in the heart than in the brain
-
isoform BB (brain) is the predominant isozyme expressed in enteric glial cells and rare neurons of the myenteric and submucosal plexuses. Isoform MM (muscle) appears in cells which are, according to their location and morphology, probably interstitial cells of Cajal. Both glycogen phosphorylase isoforms are expressed in longitudinal and circular intestinal smooth muscle layers
-
isoform BB (brain) is the predominant isozyme expressed in enteric glial cells
-
one h after the onset of pilocarpineinduced status, staining of active glycogen phosphorylase is reduced in most regions of the hippocampus and entorhinal cortex relative to saline-injected controls. One week after status, there is increased active glycogen phosphorylase and total glycogen phosphorylase, especially in the inner molecular layer, where synaptic reorganization of granule cell mossy fibre axons occurs
-
isoform MM (muscle) appears in cells which are, according to their location and morphology, probably interstitial cells of Cajal
-
muscle isoenzyme and brain isoenzyme and their respective mRNAs are found in kidney homogenates. The brain isoenzyme is immunocytochemically detected in collecting ducts which are identified by the marker protein aquaporin-2. The muscle isoenzyme is localized exclusively in interstitial cells of cortex and outer medulla
-
vagus nerve, ubiquitous presence of glycogen phosphorylase isoform BB, but not muscle isoform, in the axons of spinal and sciatic nerves, but not in Schwann cells
-
isoform BB (brain) is the predominant isozyme expressed in rare neurons of the myenteric and submucosal plexuses
-
glycogen phosphorylase is present in the axons of spinal and sciatic nerves, but not in Schwann cells. Presence of the glycogen phosphorylase BB (brain) isoform, but not the MM (muscle) isoform
-
presubiculum, but not subiculum, is strongly reactive for glycogen phosphorylase. Glycogenolytic demand in Layers I and II is organized in a modular fashion and demand can be modified by brief exposure of animals to a novel holeboard
-
one h after the onset of pilocarpineinduced status, staining of active glycogen phosphorylase is reduced in most regions of the hippocampus and entorhinal cortex relative to saline-injected controls. One week after status, there is increased active glycogen phosphorylase and total glycogen phosphorylase, especially in the inner molecular layer, where synaptic reorganization of granule cell mossy fibre axons occurs
-
at the protein level, but not at the mRNA level, the content of brain isoform of glycogen phosphorylase is similar in heart and brain. MM is more abundant in the heart than in the brain. Muscle isoform of glycogen phosphorylase is more abundant in the heart than in the brain. The brain isoform is colocalized with the muscle isoform in cardiomyocytes. The muscle isoform is also detected in interstitial cells identified as fibroblasts
-
stimulation and inhibition of glycogen synthesis in hepatocytes by serotonergic mechanisms. The former effects are associated with the inactivation of phosphorylase and are counteracted by atypical antipsychotic drugs that cause hepatic insulin resistance. Antagonism of hepatic serotonergic mechanisms may be a component of the hepatic dysregulation caused by antipsychotic drugs that predispose to type 2 diabetes
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
glycogen synthase and glycogen phosphorylase are the two enzymes that control, respectively, the synthesis and degradation of this polysaccharide
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PYGL_RAT
850
0
97483
Swiss-Prot
other Location (Reliability: 3)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
side-chain modification
phosphoprotein
-
phosphorylation and dephosphorylation of the enzyme regulates its activity and is catalyzed by a phosphorylase phosphatase
phosphoprotein
-
phosphorylation and dephosphorylation of the enzyme regulates its activity and is catalyzed by a phosphorylase phosphatase and protein kinase A
side-chain modification
-
incorporation of approx. 1 mol phosphate/mol of subunit
side-chain modification
-
phosphorylation converts inactive phosphorylase b into active phosphorylase a
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
heart isozymes I and II, ammonium sulfate, DEAE-Sephacel, AMP-Sepharose, muscle enzyme, ammonium sulfate, DEAE-Sephacel
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
overexpression of the muscle isozyme in hepatocytes, causes dissociation of glycogen synthase from proteoglycogen leading to inhibition of initiation of glycogen synthesis
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
the enzyme is an important target for is a validated target for the development of type 2 diabetes treatments and the discovery of hypoglycaemic agents, both synthetic and natural
drug development
the enzyme glycogen phosphorylase constitutes an adequate pharmacological target to modulate cellular glycogen levels, by means of inhibition of its catalytic activity
medicine
medicine
-
presubiculum, but not subiculum, of entorhinal cortex, is strongly reactive for glycogen phosphorylase. Glycogenolytic demand in Layers I and II is organized in a modular fashion and demand can be modified by brief exposure of animals to a novel holeboard
medicine
-
glycogen phosphorylase inhibitory flavonoids have potential to contribute to the protection or improvement of control of diabetes type II
medicine
-
inhibition of the liver glycogen targeting subunit/glycogen phosphorylase interaction may provide an attractive approach for rebalancing the disturbed glycogen metabolism in diabetic patients (prevention of the GLGP interaction increases the glycogen synthesis rate)
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Berndt, N.; Rosen, P.
Isolation and partial characterization of two forms of rat heart glycogen phosphorylase
Arch. Biochem. Biophys.
228
143-154
1984
Rattus norvegicus
Tavridou, A.; Agius, L.
Phosphorylase regulates the association of glycogen synthase with a proteoglycogen substrate in hepatocytes
FEBS Lett.
551
87-91
2003
Rattus norvegicus
Boer, P.; Sperling, O.
Modulation of glycogen phosphorylase activity affects 5-phosphoribosyl-1-pyrophosphate availability in rat hepatocyte cultures
Nucleosides Nucleotides Nucleic Acids
23
1235-1239
2004
Rattus norvegicus
Ercan-Fang, N.; Taylor, M.R.; Treadway, J.L.; Levy, C.B.; Genereux, P.E.; Gibbs, E.M.; Rath, V.L.; Kwon, Y.; Gannon, M.C.; Nuttall, F.Q.
Endogenous effectors of human liver glycogen phosphorylase modulate effects of indole-site inhibitors
Am. J. Physiol. Endocrinol. Metab.
289
E366-E372
2005
Homo sapiens, Mus musculus, Rattus norvegicus
Dudash, J.; Zhang, Y.; Moore, J.B.; Look, R.; Liang, Y.; Beavers, M.P.; Conway, B.R.; Rybczynski, P.J.; Demarest, K.T.
Synthesis and evaluation of 3-anilino-quinoxalinones as glycogen phosphorylase inhibitors
Bioorg. Med. Chem. Lett.
15
4790-4793
2005
Rattus norvegicus
Pfeiffer-Guglielmi, B.; Coles, J.A.; Francke, M.; Reichenbach, A.; Fleckenstein, B.; Jung, G.; Nicaise, G.; Hamprecht, B.
Immunocytochemical analysis of rat vagus nerve by antibodies against glycogen phosphorylase isozymes
Brain Res.
1110
23-29
2006
Rattus norvegicus
Walling, S.G.; Bromley, K.; Harley, C.W.
Glycogen phosphorylase reactivity in the entorhinal complex in familiar and novel environments: evidence for labile glycogenolytic modules in the rat
J. Chem. Neuroanat.
31
108-113
2006
Rattus norvegicus
Zibrova, D.; Grempler, R.; Streicher, R.; Kauschke, S.G.
Inhibition of the interaction between protein phosphatase 1 glycogen-targeting subunit and glycogen phosphorylase increases glycogen synthesis in primary rat hepatocytes
Biochem. J.
412
359-366
2008
Rattus norvegicus
Pfeiffer-Guglielmi, B.; Francke, M.; Reichenbach, A.; Hamprecht, B.
Glycogen phosphorylase isozymes and energy metabolism in the rat peripheral nervous system--an immunocytochemical study
Brain Res.
1136
20-27
2007
Rattus norvegicus
Hampson, L.J.; Mackin, P.; Agius, L.
Stimulation of glycogen synthesis and inactivation of phosphorylase in hepatocytes by serotonergic mechanisms, and counter-regulation by atypical antipsychotic drugs
Diabetologia
50
1743-1751
2007
Rattus norvegicus
Walling, S.G.; Rigoulot, M.A.; Scharfman, H.E.
Acute and chronic changes in glycogen phosphorylase in hippocampus and entorhinal cortex after status epilepticus in the adult male rat
Eur. J. Neurosci.
26
178-189
2007
Rattus norvegicus
Kato, A.; Nasu, N.; Takebayashi, K.; Adachi, I.; Minami, Y.; Sanae, F.; Asano, N.; Watson, A.A.; Nash, R.J.
Structure-activity relationships of flavonoids as potential inhibitors of glycogen phosphorylase
J. Agric. Food Chem.
56
4469-4473
2008
Rattus norvegicus
Schmid, H.; Dolderer, B.; Thiess, U.; Verleysdonk, S.; Hamprecht, B.
Renal expression of the brain and muscle isoforms of glycogen phosphorylase in different cell types
Neurochem. Res.
33
2575-2582
2008
Rattus norvegicus
Pfeiffer-Guglielmi, B.; Francke, M.; Roski, C.; Hanani, M.; Reichenbach, A.; Hamprecht, B.
Immunohistochemical localization of glycogen phosphorylase isozymes in the rat gastrointestinal muscle layers and enteric nervous system
Neurochem. Res.
34
876-883
2009
Rattus norvegicus
Parmenopoulou, V.; Kantsadi, A.L.; Tsirkone, V.G.; Chatzileontiadou, D.S.; Manta, S.; Zographos, S.E.; Molfeta, C.; Archontis, G.; Agius, L.; Hayes, J.M.; Leonidas, D.D.; Komiotis, D.
Structure based inhibitor design targeting glycogen phosphorylase B. Virtual screening, synthesis, biochemical and biological assessment of novel N-acyl-beta-D-glucopyranosylamines
Bioorg. Med. Chem.
22
4810-4825
2014
Oryctolagus cuniculus (P00489), Rattus norvegicus (P09811), Rattus norvegicus Wistar (P09811)
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