Glycogen biosynthesis (UDP-glucose → glycogen) — GSD 0/IV/XV, UGP2-DEE

Glycogen biosynthesis is the cytosolic pathway that builds the branched glucose polymer glycogen from the activated sugar donor UDP-glucose, storing glucose for later mobilisation. Four steps: UDP-glucose pyrophosphorylase (UGP2) activates glucose-1-phosphate with UTP to form UDP-glucose + pyrophosphate; glycogenin (GYG1) primes synthesis by autoglucosylating a specific tyrosine, using UDP-glucose to build a short covalently-attached alpha-1,4-glucan (~8-12 residues) that nucleates the granule; glycogen synthase (muscle GYS1, liver GYS2) then elongates the chain by processively adding UDP-glucose-derived glucose units in alpha-1,4 linkage; and the glycogen branching enzyme (GBE1) transfers ~6-7-residue segments to internal positions via alpha-1,6 linkages, creating the branches that make glycogen soluble and multiply the non-reducing ends for both synthesis and later degradation. Glycogen synthase is the rate-controlling, tightly regulated step (inhibited by phosphorylation, allosterically activated by glucose-6-phosphate). Inherited defects define disorders across the pathway: UGP2 deficiency causes a developmental and epileptic encephalopathy; GYG1 deficiency causes glycogen storage disease type XV (polyglucosan-body myopathy/cardiomyopathy); GYS2 deficiency causes hepatic glycogen storage disease type 0a (fasting ketotic hypoglycemia) and GYS1 deficiency muscle GSD 0b (cardiomyopathy, sudden death); and GBE1 deficiency causes GSD type IV (Andersen disease) and adult polyglucosan body disease — accumulation of poorly branched, amylopectin-like polyglucosan.

MODULE:glycogen_biosynthesisDRAFTMetabolic Pathwaymodules/glycogen_biosynthesis.yaml
glycogen biosynthetic processGO:0005978
GO:0005978
glycogen biosynthetic process
The module is grounded in the GO glycogen biosynthetic process (GO:0005978): UDP-glucose supply (UGP2), priming (GYG1), elongation (GYS1/GYS2) and branching (GBE1).
Reactome:R-HSA-3322077
Glycogen synthesis
Step order and reaction stoichiometries follow the human Reactome "Glycogen synthesis" reactions R-HSA-70286 (UGP2), R-HSA-3322025 (GYG1 autoglucosylation), R-HSA-3322001 (GYS1) / R-HSA-3322009 (GYS2) and R-HSA-3322005 (GBE1 branch formation).
file:human/UGP2/UGP2-ai-review.yaml
UGP2 gene review (human)
The UDP-glucose supply step (UniProtKB:Q16851, GO:0003983) matches the completed human UGP2 review.
file:human/GYG1/GYG1-ai-review.yaml
GYG1 gene review (human)
The glycogenin priming step (UniProtKB:P46976, GO:0008466) matches the completed human GYG1 review.
file:human/GYS1/GYS1-ai-review.yaml
GYS1 gene review (human)
The muscle glycogen-synthase elongation step (UniProtKB:P13807, GO:0004373) matches the completed human GYS1 review.
file:human/GYS2/GYS2-ai-review.yaml
GYS2 gene review (human)
The liver glycogen-synthase elongation step (UniProtKB:P54840, GO:0004373) matches the completed human GYS2 review.
file:human/GBE1/GBE1-ai-review.yaml
GBE1 gene review (human)
The alpha-1,6 branch-formation step (UniProtKB:Q04446, GO:0003844) matches the completed human GBE1 review.
5Nodes
4Parts
0Variant Sets
0Variants
4Annotons
5Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:glycogen_biosynthesis deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

5 gene-function check(s) reflected in core functions · 0 conflict(s) · 2 evidence or coverage gap(s) (9 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
ugp2_activity UGP2 (human)
UniProtKB:Q16851
Family Representative 		UTP:glucose-1-phosphate uridylyltransferase activity
GO:0003983 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gyg1_activity GYG1 (human)
UniProtKB:P46976
Family Representative 		glycogenin glucosyltransferase activity
GO:0008466 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gys_activity GYS1 (human, muscle isoform)
UniProtKB:P13807
Family Representative 		alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity
GO:0004373 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gys_activity GYS2 (human, liver isoform)
UniProtKB:P54840
Family Representative 		alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity
GO:0004373 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gbe1_activity GBE1 (human)
UniProtKB:Q04446
Family Representative 		1,4-alpha-glucan branching enzyme activity
GO:0003844 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ugp2_activity UTP:glucose-1-phosphate uridylyltransferase family (UGP2)
PANTHER:PTHR43511
Family 		UTP:glucose-1-phosphate uridylyltransferase activity
GO:0003983 		Family Supported
Family review supports GO:0003983 FAMILY_WIDE. This is the defining activity of the eukaryotic UDPGP type 1 family. All four modules that use the family assert it, with catalytic representatives: dolichol_phosphate_sugar_donor_supply (as SF4, with UGP1, fyu1 and UGP2), glycogen_metabolism_fungal (UGP1, UGP2), and glycogen_biosynthesis (UGP2). The only exception is the S. pombe paralog SPCC794.10, which PAINT records as diverged.
gyg1_activity Glycogenin family (GYG1/GYG2)
PANTHER:PTHR11183
Family 		glycogenin glucosyltransferase activity
GO:0008466 		Family Scope Restricted
GO:0008466 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Glycogenins only. glycogen_metabolism_fungal and glycogen_biosynthesis select the base family, which also takes in galactinol synthases, GUX and GNT1. Subfamily placements are from the PANTHER 19 classification files; the cached entries carry none.
gys_activity Glycogen synthase family (GYS1/GYS2)
PANTHER:PTHR10176
Family 		alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activity
GO:0004373 		Family Supported
Family review supports GO:0004373 FAMILY_WIDE. Asserted by glycogen_metabolism_fungal and glycogen_biosynthesis on the base family; accepted by every reviewed member in all three subfamilies.
gbe1_activity 1,4-alpha-glucan branching enzyme family (GBE1)
PANTHER:PTHR43651
Family 		1,4-alpha-glucan branching enzyme activity
GO:0003844 		Family Scope Restricted
GO:0003844 is SUBFAMILY_ONLY; this family grounding does not establish the allowed subfamily scope. Asserted by glycogen_metabolism_fungal, glycogen_biosynthesis, tres_mak_glge_branched_alpha_glucan_biosynthesis and glycogen_synthesis_and_mobilization; accepted by GLC3. Restricted to the branching-enzyme clade PTN000040010; TreZ (SF11) lacks it.

Gene-review completeness (5/5 grounded genes reviewed)

4 complete review(s) · 0 with deep research · 0 missing review · 5 reviewed but lacking deep research

Gene Review Complete Deep research
GBE1 Q04446 ✓ 27/28 ✗
GYG1 P46976 ✓ ✓ ✗
GYS1 P13807 ✓ ✓ ✗
GYS2 P54840 ✓ ✓ ✗
UGP2 Q16851 ✓ ✓ ✗

Details

Context
cytosolGO:0005829
Glycogen biosynthesisMetabolic Pathwayglycogen_biosynthesis
glycogen biosynthetic processGO:0005978
Context
cytosolGO:0005829

Four-step cytosolic glycogen biosynthesis grounded to the human enzymes UGP2 (UniProtKB:Q16851; GO:0003983, EC 2.7.7.9), glycogenin GYG1 (P46976; GO:0008466, EC 2.4.1.186), glycogen synthase GYS1 (P13807) / GYS2 (P54840) (GO:0004373, EC 2.4.1.11) and branching enzyme GBE1 (Q04446; GO:0003844, EC 2.4.1.18). GO molecular-function terms were taken from the human GOA records; Reactome reaction ids and titles were verified against the local reactome cache. The glycogen-synthase step uses a PANTHER family selector (PTHR10176) generic over GYS1/GYS2 and orthologs, with both human isoforms as representative members; GYG1 (PTHR11183, family also includes GYG2), UGP2 (PTHR43511) and GBE1 (PTHR43651) likewise use family selectors plus a human representative. This is the biosynthetic counterpart of the glycogenolysis module (PYGL/PYGM, AGL, PGM1): glucose-1-phosphate is the shared branch metabolite (PGM1 links the two directions), and glycogenin/synthase form the granule that phosphorylase later degrades. UGP2's UDP-glucose also feeds galactose (Leloir) metabolism and glycosylation (noted, out of scope here). Disorders: UGP2 -> DEE83; GYG1 -> GSD XV; GYS1 -> muscle GSD 0b; GYS2 -> liver GSD 0a; GBE1 -> GSD IV (Andersen) / adult polyglucosan body disease.

Connections

ugp2_step -> gyg1_step Provides Input For
UDP-glucose from UGP2 is the donor for glycogenin autoglucosylation.
ugp2_step -> gys_step Provides Input For
UDP-glucose from UGP2 is the donor for glycogen-synthase elongation.
gyg1_step -> gys_step Provides Input For
The oligoglucosyl-glycogenin primer is the substrate that glycogen synthase elongates.
gys_step -> gbe1_step Provides Input For
The linear alpha-1,4 chains made by glycogen synthase are branched by GBE1.
gbe1_step -> gys_step Provides Input For
Branching multiplies the non-reducing ends, which glycogen synthase continues to elongate (the synthase/branching cycle).
Part 1: activation of glucose-1-phosphate to the UDP-glucose donor
glucose-1-phosphate + UTP to UDP-glucose + diphosphateReactionugp2_step

Annotons

UGP2: UDP-glucose pyrophosphorylase
ugp2_activity
Participant: Family: UTP:glucose-1-phosphate uridylyltransferase family (UGP2)
Family:
UTP:glucose-1-phosphate uridylyltransferase family (UGP2)PANTHER:PTHR43511
Representative Members: UGP2 (human)UniProtKB:Q16851

Function

UTP:glucose-1-phosphate uridylyltransferase activityGO:0003983
Substrates: alpha-D-glucose 1-phosphate UTP
Products: UDP-alpha-D-glucose diphosphate

Locations

cytosolGO:0005829

Provides UDP-glucose, the activated glucosyl donor for glycogen synthesis (and for galactose/Leloir metabolism, glycosylation and glucuronidation). Deficiency causes developmental and epileptic encephalopathy 83.

Part 2: priming / initiation (self-glucosylating primer)
glycogenin + n UDP-glucose to oligoglucosyl-glycogenin primer + n UDPReactiongyg1_step

Annotons

GYG1: glycogenin (self-glucosylating initiator)
gyg1_activity
Participant: Family: Glycogenin family (GYG1/GYG2)
Family:
Glycogenin family (GYG1/GYG2)PANTHER:PTHR11183
Representative Members: GYG1 (human)UniProtKB:P46976

Function

glycogenin glucosyltransferase activityGO:0008466
Substrates: glycogenin (Tyr acceptor) UDP-alpha-D-glucose
Products: oligo(1,4-alpha-glucosyl)-glycogenin primer UDP

Locations

cytosolGO:0005829

Mn2+-dependent, self-glucosylating initiator: builds a short covalently attached alpha-1,4-glucan primer (~8-12 residues on a Tyr) that nucleates the glycogen granule and is elongated by glycogen synthase (with which it forms a complex). Deficiency causes GSD XV (polyglucosan-body myopathy).

Part 3: processive alpha-1,4 elongation (rate-controlling)
glycogen(n) + UDP-glucose to glycogen(n+1) + UDPReactiongys_step

Annotons

GYS1/GYS2: glycogen synthase
gys_activity
Participant: Family: Glycogen synthase family (GYS1/GYS2)
Family:
Glycogen synthase family (GYS1/GYS2)PANTHER:PTHR10176
Representative Members: GYS1 (human, muscle isoform)UniProtKB:P13807 GYS2 (human, liver isoform)UniProtKB:P54840

Function

alpha-1,4-glucan glucosyltransferase (UDP-glucose donor) activityGO:0004373
Substrates: glycogen (alpha-1,4 non-reducing ends) UDP-alpha-D-glucose
Products: elongated glycogen(n+1) UDP

Locations

cytosolGO:0005829

Rate-controlling, allosterically- and phosphorylation-regulated enzyme that processively elongates the alpha-1,4 chains from the glycogenin primer using UDP-glucose. Tissue isoforms: GYS1 (muscle, GSD 0b) and GYS2 (liver, GSD 0a).

Part 4: introduction of alpha-1,6 branches
linear alpha-1,4-glucan to alpha-1,6-branched glycogenReactiongbe1_step

Annotons

GBE1: 1,4-alpha-glucan branching enzyme
gbe1_activity
Participant: Family: 1,4-alpha-glucan branching enzyme family (GBE1)
Family:
1,4-alpha-glucan branching enzyme family (GBE1)PANTHER:PTHR43651
Representative Members: GBE1 (human)UniProtKB:Q04446

Function

1,4-alpha-glucan branching enzyme activityGO:0003844
Substrates: linear alpha-1,4-glucan chain
Products: alpha-1,6-branched glycogen

Locations

cytosolGO:0005829

Introduces the alpha-1,6 branch points by transferring ~6-7-residue segments from a growing alpha-1,4 chain to internal positions, increasing solubility and the number of non-reducing ends. Deficiency causes GSD IV (Andersen disease) and adult polyglucosan body disease.