GLYCOGEN DEGRADATION PATHWAY (PW:0000534)
Description
Glycogenolysis is the degradation
pathway of glycogen - a ramified
polysaccharide formed by alpha1-4 linked glucose units branching at alpha1-6 bonds - to G6P, a key molecule at the
intersection of several pathways of glucose metabolism. In muscle, glycogenolysis
is used to provide energy whereas liver glycogenolysis is used to supply
glucose to extrahepatic tissues and organs (brain is a good example - it relies
on glucose as an energy source while having a limited capacity for storing it).
Glycogen phosphorylases - pyridoxal-5 phosphate-dependent enzymes - catalyze
the first and rate-limiting step of glycogenolysis to produce glucose-1-phosphate,
which is converted to G6P via the reversible reaction carried out by
phosphoglucomutases (Pgm). The alpha1-4 cleavage carried out by
phosphorylases continues for as long as the glycogen chain is at least four to five residues
from a branch point. The glycogen debranching enzyme (Agl) catalyzes the
transfer of three glucose units to an adjacent branch; a second glucosidase
reaction cleaves the alpha1-6 bond and removes the glucose unit
from the branch point so that the phosphorylase activity can resume. In
mammals, there are three phosphorylase isoforms - the muscle-, liver- and brain-
specific enzymes; they are similarly regulated by covalent modification but are
differently sensitive to allosteric regulation. The enzymes are dimers which in
the resting state are in an inactive conformation. Phosphorylation of a single
residue by phosphorylase kinase promotes a conformational change to the active
state. Phosphorylase kinase is composed of four non-identical subunits of which
the gamma subunit is the catalytic unit and the other three - alpha, beta and delta
- are regulatory. Maximal activation of phosphorylase kinase is achieved by
phosphorylation of the alpha and beta subunits by protein kinase A and by
calcium binding to the delta subunit, which is calmodulin. Protein phosphatase 1
(Pp-1) dephosphorylates and inactivates both the phosphorylase kinase and
glycogen phosphorylase enzymes. Note that this is also the phosphatase that
dephosphorylates and activates glycogen synthase, the key enzyme of the glycogen
biosynthetic pathway. G6P, which is an allosteric activator of glycogen
synthase, acts as an allosteric inhibitor of glycogen phosphorylase. Thus, the
two arms of glycogen metabolism are closely regulated at the level of the key
enzymes involved in them.
To see the ontology report for annotations, GViewer and download click here [click to see
the ontology report for associated GO term - GO:0005980 and entry at Reactome -
REACT_1008.1 ]
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Pathway Diagram:
Genes in Pathway:
G
Agl amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase
IDA IMP RGD
PMID:15180797 PMID:11766064 RGD:1642741 , RGD:2304191
NCBI chr 2:204,705,053...204,760,966
G
Calm1 calmodulin 1
ISO RGD
PMID:10487978 RGD:2305981
NCBI chr 6:119,487,691...119,495,759
G
Calm2 calmodulin 2
ISO RGD
PMID:10487978 RGD:2305981
NCBI chr 6:7,091,624...7,104,284
G
Calm3 calmodulin 3
ISO RGD
PMID:10487978 RGD:2305981
NCBI chr 1:77,590,668...77,597,776
G
Pgm1 phosphoglucomutase 1
ISO RGD
PMID:9549096 RGD:2304188
NCBI chr 5:114,595,298...114,654,728
G
Pgm2 phosphoglucomutase 2
ISO RGD
PMID:9549096 RGD:2304188
NCBI chr14:44,166,314...44,199,828
G
Pgm3 phosphoglucomutase 3
ISO RGD
PMID:9549096 RGD:2304188
NCBI chr 8:87,518,317...87,536,021
G
Phka1 phosphorylase kinase regulatory subunit alpha 1
ISO RGD
PMID:10487978 RGD:2305981
NCBI chr X:67,601,302...67,738,504
G
Phka2 phosphorylase kinase regulatory subunit alpha 2
ISO RGD
PMID:10487978 RGD:2305981
NCBI chr X:34,170,959...34,293,498
G
Phkb phosphorylase kinase regulatory subunit beta
ISO RGD
PMID:10487978 RGD:2305981
NCBI chr19:21,013,719...21,210,671
G
Phkg1 phosphorylase kinase catalytic subunit gamma 1
ISO RGD
PMID:10487978 RGD:2305981
NCBI chr12:26,838,822...26,854,547
G
Phkg2 phosphorylase kinase catalytic subunit gamma 2
ISO RGD
PMID:10487978 RGD:2305981
NCBI chr 1:182,184,362...182,197,124
G
Ppp1ca protein phosphatase 1 catalytic subunit alpha
ISO IDA RGD
PMID:14715909 PMID:7720853 RGD:2304325 , RGD:2304267
NCBI chr 1:201,485,117...201,488,734
G
Ppp1cb protein phosphatase 1 catalytic subunit beta
ISO IDA RGD
PMID:14715909 PMID:7720853 RGD:2304325 , RGD:2304267
NCBI chr 6:23,958,813...23,992,841
G
Ppp1cc protein phosphatase 1 catalytic subunit gamma
ISO RGD
PMID:14715909 RGD:2304325
NCBI chr12:34,383,072...34,400,553
G
Ppp1r3a protein phosphatase 1, regulatory subunit 3A
ISO RGD
PMID:14715909 RGD:2304325
NCBI chr 4:42,937,353...42,980,195
G
Ppp1r3b protein phosphatase 1, regulatory subunit 3B
ISO IDA RGD
PMID:14715909 PMID:7720853 PMID:11716774 RGD:2304325 , RGD:2304267 , RGD:2306167
NCBI chr16:56,830,011...56,842,395
G
Ppp1r3c protein phosphatase 1, regulatory subunit 3C
IDA RGD
PMID:11716774 RGD:2306167
NCBI chr 1:234,460,958...234,465,961
G
Ppp1r3d protein phosphatase 1, regulatory subunit 3D
IDA RGD
PMID:11716774 RGD:2306167
NCBI chr 3:165,502,384...165,505,455
G
Ppp1r3e protein phosphatase 1, regulatory subunit 3E
IDA RGD
PMID:15752363 RGD:2306166
NCBI chr15:28,348,443...28,349,603
G
Pygb glycogen phosphorylase B
ISO RGD
PMID:11340058 PMID:1544539 RGD:1642822 , RGD:2304109
NCBI chr 3:139,611,724...139,658,521
G
Pygl glycogen phosphorylase L
IDA ISO RGD
PMID:15138155 PMID:16125296 PMID:11340058 PMID:1544539 RGD:1582633 , RGD:1601233 , RGD:1642822 , RGD:2304109
NCBI chr 6:88,697,598...88,740,260
G
Pygm glycogen phosphorylase, muscle associated
ISO IDA RGD
PMID:11340058 PMID:1544539 PMID:11692172 RGD:1642822 , RGD:2304109 , RGD:1599897
NCBI chr 1:203,690,550...203,705,369
Pathway Gene Annotations
Disease Annotations Associated with Genes in the glycogen degradation pathway
Agl Arthrogryposis, Impaired Intellectual Development, and Seizures , Experimental Liver Cirrhosis , genetic disease , glycogen storage disease , glycogen storage disease III , Glycogen Storage Disease IIIA , Glycogen Storage Disease IIIB , Glycogen Storage Disease IIIC , maple syrup urine disease , Myocardial Reperfusion Injury , uremia Calm1 achondrogenesis type IA , Alzheimer's disease , cannabis abuse , catecholaminergic polymorphic ventricular tachycardia , catecholaminergic polymorphic ventricular tachycardia 1 , catecholaminergic polymorphic ventricular tachycardia 4 , Cocaine-Related Disorders , Familial Ventricular Tachycardia , long QT syndrome 14 , phencyclidine abuse , type 2 diabetes mellitus , Weight Gain Calm2 cannabis abuse , Cocaine-Related Disorders , COVID-19 , genetic disease , long QT syndrome , long QT syndrome 1 , long QT syndrome 15 , Lynch syndrome , major depressive disorder , multiple intestinal atresia , phencyclidine abuse , sudden infant death syndrome Calm3 familial hypertrophic cardiomyopathy , long QT syndrome , long QT syndrome 1 , long QT syndrome 16 , Walker-Warburg syndrome Pgm1 Chemical and Drug Induced Liver Injury , Colorectal Neoplasms , congenital disorder of glycosylation , congenital disorder of glycosylation It , Craniosynostosis Syndrome, Autosomal Recessive , endometrial cancer , genetic disease , intellectual disability , Myocardial Ischemia , teratoma Pgm2 COVID-19 , genetic disease Pgm3 cervical cancer , genetic disease , hyper IgE syndrome , immunodeficiency 23 , severe combined immunodeficiency , teratoma Phka1 autistic disorder , Cornelia de Lange syndrome 5 , Experimental Diabetes Mellitus , genetic disease , glycogen storage disease , glycogen storage disease IXD , hypothyroidism , intestinal volvulus , neuropathy , peripheral nervous system disease , syndromic X-linked intellectual disability Lubs type , Volvulus Of Midgut , X-linked spinocerebellar ataxia 1 Phka2 autistic disorder , Coffin-Lowry syndrome , developmental and epileptic encephalopathy 2 , genetic disease , glycogen storage disease , glycogen storage disease IXA , glycogen storage disease IXD , glycogen storage disease VIII , Nance-Horan syndrome , Neurodevelopmental Disorders , Pyruvate Dehydrogenase E1 Alpha Deficiency , syndromic X-linked intellectual disability Lubs type Phkb genetic disease , glycogen storage disease IXB Phkg1 autistic disorder , genetic disease , pleomorphic xanthoastrocytoma , PSPH deficiency Phkg2 branched-chain keto acid dehydrogenase kinase deficiency , Fibrosis , generalized epilepsy with febrile seizures plus 9 , genetic disease , glycogen storage disease , glycogen storage disease IXC , liver cirrhosis , Mauriac Syndrome Ppp1ca Aicardi-Goutieres Syndrome 3 , congestive heart failure , dilated cardiomyopathy , genetic disease , intellectual disability , Recurrent Infections, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations Ppp1cb Dandy-Walker syndrome , genetic disease , Noonan syndrome , Noonan syndrome-like disorder with loose anagen hair 2 , Tatton-Brown-Rahman syndrome Ppp1cc congestive heart failure , genetic disease , Ovarian Neoplasms , Spinal Cord Injuries Ppp1r3a diabetes mellitus , genetic disease , hypoglycemia , Insulin Resistance , maturity-onset diabetes of the young type 1 , Neurodevelopmental Disorders , pleomorphic xanthoastrocytoma , type 2 diabetes mellitus Ppp1r3b Experimental Liver Cirrhosis , genetic disease , Neurodevelopmental Disorders Ppp1r3c Experimental Liver Cirrhosis , genetic disease , prostate cancer , type 2 diabetes mellitus Ppp1r3d genetic disease Ppp1r3e Brain-Lung-Thyroid Syndrome , lysinuric protein intolerance , Specific Granule Deficiency Pygb adenoid cystic carcinoma , Dwarfism , genetic disease , Myocardial Ischemia , Salivary Gland Neoplasms Pygl Chemical and Drug Induced Liver Injury , genetic disease , glycogen storage disease , glycogen storage disease VI , hepatocellular carcinoma , Hepatomegaly , lactic acidosis Pygm Bardet-Biedl syndrome , Cardiomegaly , cholestasis , Experimental Diabetes Mellitus , genetic disease , glycogen storage disease V , high grade glioma , High Myopia , intellectual disability , isolated elevated serum creatine phosphokinase levels , leukocyte adhesion deficiency 3 , muscular atrophy , muscular disease , Myocardial Ischemia , myopathy , Paralysis , Rhabdomyolysis
achondrogenesis type IA Calm1 adenoid cystic carcinoma Pygb Aicardi-Goutieres Syndrome 3 Ppp1ca Alzheimer's disease Calm1 Arthrogryposis, Impaired Intellectual Development, and Seizures Agl autistic disorder Phka1 , Phka2 , Phkg1 Bardet-Biedl syndrome Pygm Brain-Lung-Thyroid Syndrome Ppp1r3e branched-chain keto acid dehydrogenase kinase deficiency Phkg2 cannabis abuse Calm1 , Calm2 Cardiomegaly Pygm catecholaminergic polymorphic ventricular tachycardia Calm1 catecholaminergic polymorphic ventricular tachycardia 1 Calm1 catecholaminergic polymorphic ventricular tachycardia 4 Calm1 cervical cancer Pgm3 Chemical and Drug Induced Liver Injury Pgm1 , Pygl cholestasis Pygm Cocaine-Related Disorders Calm1 , Calm2 Coffin-Lowry syndrome Phka2 Colorectal Neoplasms Pgm1 congenital disorder of glycosylation Pgm1 congenital disorder of glycosylation It Pgm1 congestive heart failure Ppp1ca , Ppp1cc Cornelia de Lange syndrome 5 Phka1 COVID-19 Calm2 , Pgm2 Craniosynostosis Syndrome, Autosomal Recessive Pgm1 Dandy-Walker syndrome Ppp1cb developmental and epileptic encephalopathy 2 Phka2 diabetes mellitus Ppp1r3a dilated cardiomyopathy Ppp1ca Dwarfism Pygb endometrial cancer Pgm1 Experimental Diabetes Mellitus Phka1 , Pygm Experimental Liver Cirrhosis Agl , Ppp1r3b , Ppp1r3c familial hypertrophic cardiomyopathy Calm3 Familial Ventricular Tachycardia Calm1 Fibrosis Phkg2 generalized epilepsy with febrile seizures plus 9 Phkg2 genetic disease Agl , Calm2 , Pgm1 , Pgm2 , Pgm3 , Phka1 , Phka2 , Phkb , Phkg1 , Phkg2 , Ppp1ca , Ppp1cb , Ppp1cc , Ppp1r3a , Ppp1r3b , Ppp1r3c , Ppp1r3d , Pygb , Pygl , Pygm glycogen storage disease Agl , Phka1 , Phka2 , Phkg2 , Pygl glycogen storage disease III Agl Glycogen Storage Disease IIIA Agl Glycogen Storage Disease IIIB Agl Glycogen Storage Disease IIIC Agl glycogen storage disease IXA Phka2 glycogen storage disease IXB Phkb glycogen storage disease IXC Phkg2 glycogen storage disease IXD Phka1 , Phka2 glycogen storage disease V Pygm glycogen storage disease VI Pygl glycogen storage disease VIII Phka2 hepatocellular carcinoma Pygl Hepatomegaly Pygl high grade glioma Pygm High Myopia Pygm hyper IgE syndrome Pgm3 hypoglycemia Ppp1r3a hypothyroidism Phka1 immunodeficiency 23 Pgm3 Insulin Resistance Ppp1r3a intellectual disability Pgm1 , Ppp1ca , Pygm intestinal volvulus Phka1 isolated elevated serum creatine phosphokinase levels Pygm lactic acidosis Pygl leukocyte adhesion deficiency 3 Pygm liver cirrhosis Phkg2 long QT syndrome Calm2 , Calm3 long QT syndrome 1 Calm2 , Calm3 long QT syndrome 14 Calm1 long QT syndrome 15 Calm2 long QT syndrome 16 Calm3 Lynch syndrome Calm2 lysinuric protein intolerance Ppp1r3e major depressive disorder Calm2 maple syrup urine disease Agl maturity-onset diabetes of the young type 1 Ppp1r3a Mauriac Syndrome Phkg2 multiple intestinal atresia Calm2 muscular atrophy Pygm muscular disease Pygm Myocardial Ischemia Pgm1 , Pygb , Pygm Myocardial Reperfusion Injury Agl myopathy Pygm Nance-Horan syndrome Phka2 Neurodevelopmental Disorders Phka2 , Ppp1r3a , Ppp1r3b neuropathy Phka1 Noonan syndrome Ppp1cb Noonan syndrome-like disorder with loose anagen hair 2 Ppp1cb Ovarian Neoplasms Ppp1cc Paralysis Pygm peripheral nervous system disease Phka1 phencyclidine abuse Calm1 , Calm2 pleomorphic xanthoastrocytoma Phkg1 , Ppp1r3a prostate cancer Ppp1r3c PSPH deficiency Phkg1 Pyruvate Dehydrogenase E1 Alpha Deficiency Phka2 Recurrent Infections, with Encephalopathy, Hepatic Dysfunction, and Cardiovascular Malformations Ppp1ca Rhabdomyolysis Pygm Salivary Gland Neoplasms Pygb severe combined immunodeficiency Pgm3 Specific Granule Deficiency Ppp1r3e Spinal Cord Injuries Ppp1cc sudden infant death syndrome Calm2 syndromic X-linked intellectual disability Lubs type Phka1 , Phka2 Tatton-Brown-Rahman syndrome Ppp1cb teratoma Pgm1 , Pgm3 type 2 diabetes mellitus Calm1 , Ppp1r3a , Ppp1r3c uremia Agl Volvulus Of Midgut Phka1 Walker-Warburg syndrome Calm3 Weight Gain Calm1 X-linked spinocerebellar ataxia 1 Phka1
