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GLYCOGEN BIOSYNTHETIC PATHWAY (PW:0000532)
DescriptionGlycogen - the storage form of glucose - is a ramified
polysaccharide formed by alpha1-4
linked glucose units branching at alpha1-6
bonds. Upon uptake into the cell, glucose is rapidly phosphorylated to G6P, a
key molecule at the intersection of several pathways of glucose metabolism. In
the glycogen biosynthetic pathway, G6P is converted to G1P via the reversible
reaction carried out by phosphoglucomutases (Pgm). UDP-glucose
pyrophosphorylase (Ugp2) catalyzes the formation of UDP-glucose by combining
G1P and UTP; hydrolysis of Ppi by the inorganic pyrophosphatase renders the
overall reaction exergonic. The initial priming of glycogen is carried out by
the self-glucosylating protein glycogenin (Gyg). Glycogen is then extended and
branched by glycogen synthase (Gys) and the glycogen branching enzyme (Gbe1),
respectively. Glycogen synthase catalyzes the transfer of glucosyl groups from
UDP-glucose to glycogen via alpha1-4
linkage; when the elongated glycogen has at least 11 residues, the branching
enzyme transfers a chain of ~seven glucosyl groups to another chain via alpha1-6
linkage. G6P is an allosteric regulator of glycogen synthase as well as
glycogen phosphorylase, a key component of the glycogen degradation pathway. Note
that the two essential enzymes of glycogen metabolism are subject to covalent
and allosteric regulation, aspects of which cross paths in opposite directions.
Glycogen synthase is inactivated and activated by phosphorylation/dephosphorylation,
respectively. The allosteric activation by G6P involves unfolding of the
enzyme which overrides the effect of phosphorylation and conformational changes
that prime it for dephosphorylation. Several kinases, including glycogen
synthase kinase-3 (Gsk3) phosphorylate the synthase; dephosphorylation is
primarily mediated by protein phosphatase-1 (Pp-1). The phosphatase is a
complex between a catalytic subunit encoded by three genes in mammals and any
of a host of regulatory subunits that allow for the formation of a variety of
distinct multimeric holoenzymes that regulate many cellular processes. In the
case of glycogen metabolism, the glycogen or G-targeting subunits are part of
the Pp-1 complex anchored to the glycogen particles to which the key enzymes of
glycogen anabolism and catabolism are bound. Pp-1 also modifies and inactivates
glycogen phosphorylase and phosphorylase kinase; the first, as mentioned, is a
key enzyme of glycogen degradation and the second is its activator. 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:0005978 and entry at Reactome - REACT_1736.2] ...(less)
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Pathway Diagram:
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Genes in Pathway:
glycogen biosynthetic pathway
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| G |
Gbe1 |
glucan (1,4-alpha-), branching enzyme 1 |
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IDA |
11 |
8,720,408 |
8,975,471 |
RGD:1642743 |
RGD |
| G |
Gck |
glucokinase |
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IDA |
14 |
86,572,518 |
86,587,723 |
RGD:1582633 |
RGD |
| G |
Gsk3a |
glycogen synthase kinase 3 alpha |
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ISS |
1 |
80,505,517 |
80,514,139 |
RGD:2306093 |
RGD |
| G |
Gsk3b |
glycogen synthase kinase 3 beta |
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ISS |
11 |
64,284,731 |
64,428,698 |
RGD:2306093 |
RGD |
| G |
Gyg1 |
glycogenin 1 |
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IDA |
2 |
105,264,657 |
105,307,070 |
RGD:2304070 |
RGD |
| G |
Gyg1 |
glycogenin 1 |
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IDA |
2 |
105,264,657 |
105,307,070 |
RGD:2303736 |
RGD |
| G |
Gys1 |
glycogen synthase 1, muscle |
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ISS |
1 |
95,907,458 |
95,928,150 |
RGD:2304106 |
RGD |
| G |
Gys1 |
glycogen synthase 1, muscle |
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IDA |
1 |
95,907,458 |
95,928,150 |
RGD:1642743 |
RGD |
| G |
Gys2 |
glycogen synthase 2 |
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IDA |
4 |
179,984,036 |
180,018,819 |
RGD:1582633 |
RGD |
| G |
Gys2 |
glycogen synthase 2 |
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IDA |
4 |
179,984,036 |
180,018,819 |
RGD:1642743 |
RGD |
| G |
Gys2 |
glycogen synthase 2 |
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ISS |
4 |
179,984,036 |
180,018,819 |
RGD:2304106 |
RGD |
| G |
Pgm1 |
phosphoglucomutase 1 |
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ISS |
5 |
120,595,650 |
120,655,915 |
RGD:2304188 |
RGD |
| G |
Pgm2 |
phosphoglucomutase 2 |
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ISS |
14 |
46,827,166 |
46,862,298 |
RGD:2304188 |
RGD |
| G |
Pgm3 |
phosphoglucomutase 3 |
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ISS |
8 |
91,810,223 |
91,827,293 |
RGD:2304188 |
RGD |
| G |
Ppp1ca |
protein phosphatase 1, catalytic subunit, alpha isozyme |
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IDA |
1 |
206,774,719 |
206,778,336 |
RGD:2304267 |
RGD |
| G |
Ppp1ca |
protein phosphatase 1, catalytic subunit, alpha isozyme |
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ISS |
1 |
206,774,719 |
206,778,336 |
RGD:2304325 |
RGD |
| G |
Ppp1cb |
protein phosphatase 1, catalytic subunit, beta isozyme |
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IDA |
6 |
24,067,544 |
24,099,280 |
RGD:2304267 |
RGD |
| G |
Ppp1cb |
protein phosphatase 1, catalytic subunit, beta isozyme |
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ISS |
6 |
24,067,544 |
24,099,280 |
RGD:2304325 |
RGD |
| G |
Ppp1cc |
protein phosphatase 1, catalytic subunit, gamma isozyme |
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ISS |
12 |
35,580,169 |
35,598,249 |
RGD:2304325 |
RGD |
| G |
Ppp1r3a |
protein phosphatase 1, regulatory subunit 3A |
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ISS |
4 |
40,195,325 |
40,235,913 |
RGD:2304325 |
RGD |
| G |
Ppp1r3b |
protein phosphatase 1, regulatory subunit 3B |
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IDA |
16 |
60,552,431 |
60,564,789 |
RGD:2304267 |
RGD |
| G |
Ppp1r3b |
protein phosphatase 1, regulatory subunit 3B |
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ISS |
16 |
60,552,431 |
60,564,789 |
RGD:2304325 |
RGD |
| G |
Ppp1r3b |
protein phosphatase 1, regulatory subunit 3B |
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IDA |
16 |
60,552,431 |
60,564,789 |
RGD:2306167 |
RGD |
| G |
Ppp1r3c |
protein phosphatase 1, regulatory subunit 3C |
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IDA |
1 |
240,991,884 |
240,996,887 |
RGD:2306167 |
RGD |
| G |
Ppp1r3d |
protein phosphatase 1, regulatory subunit 3D |
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IDA |
3 |
167,505,678 |
167,508,749 |
RGD:2306167 |
RGD |
| G |
Ppp1r3e |
protein phosphatase 1, regulatory subunit 3E |
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IDA |
15 |
32,974,172 |
32,975,332 |
RGD:2306166 |
RGD |
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Pathway Gene Annotations |
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Disease Annotations Associated with Genes in the glycogen biosynthetic pathway
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| Gbe1 | Glycogen Storage Disease Type IV | | Gck | Coronary Artery Disease , Diabetes Mellitus , Diabetes Mellitus, Experimental , Diabetes Mellitus, Permanent Neonatal , Diabetes Mellitus, Type 2 , Diabetes, Gestational , Hyperinsulinemic hypoglycemia, familial, 3 , Hyperinsulinism , Hypertension , Hypoglycemia , Maturity-Onset Diabetes of the Young, Type 2 | |
| Gsk3b | Alzheimer Disease | | Gyg1 | GLYCOGEN STORAGE DISEASE XV | | Gys1 | Cardiovascular Diseases , Glycogen Storage Disease 0, Muscle , Insulin Resistance | | Gys2 | Glycogen Storage Disease , Glycogen Storage Disease 0, Liver | | Pgm1 | Endometrial Neoplasms , Glycogen Storage Disease XIV , Teratoma | |
| Pgm3 | Teratoma , Uterine Cervical Neoplasms | | Ppp1ca | Cardiac Output, Low , Cardiomyopathy, Dilated , Heart Failure | |
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| Ppp1r3a | Diabetes Mellitus, Type 2 , Hypoglycemia , Insulin Resistance , Lipodystrophy, Familial Partial , LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 3 , Obesity | |
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| Diabetes Mellitus | Gck | | Obesity | Ppp1r3a | | Diabetes Mellitus, Type 2 | Gck , Ppp1r3a | | Hypoglycemia | Gck , Ppp1r3a | | Teratoma | Pgm1 , Pgm3 | | Cardiomyopathy, Dilated | Ppp1ca | | Uterine Cervical Neoplasms | Pgm3 | | Alzheimer Disease | Gsk3b | | Hypertension | Gck | | Glycogen Storage Disease Type IV | Gbe1 | | Insulin Resistance | Ppp1r3a , Gys1 | | Glycogen Storage Disease | Gys2 | | Hyperinsulinemic hypoglycemia, familial, 3 | Gck | | Hyperinsulinism | Gck | | Cardiac Output, Low | Ppp1ca | | Cardiovascular Diseases | Gys1 | | Coronary Artery Disease | Gck | | Diabetes Mellitus, Experimental | Gck | | Heart Failure | Ppp1ca | | Diabetes, Gestational | Gck | | Endometrial Neoplasms | Pgm1 | | Lipodystrophy, Familial Partial | Ppp1r3a | | LIPODYSTROPHY, FAMILIAL PARTIAL, TYPE 3 | Ppp1r3a | | GLYCOGEN STORAGE DISEASE XV | Gyg1 | | Diabetes Mellitus, Permanent Neonatal | Gck | | Maturity-Onset Diabetes of the Young, Type 2 | Gck | | Glycogen Storage Disease 0, Liver | Gys2 | | Glycogen Storage Disease 0, Muscle | Gys1 | | Glycogen Storage Disease XIV | Pgm1 | |
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