Glycine cleavage system

A four-component lipoyl-relay system that oxidatively decarboxylates glycine, transfers its one-carbon unit to tetrahydrofolate, and regenerates the oxidized H-protein carrier. The P protein loads the aminomethyl intermediate onto the H protein, the H protein carries it to the T protein, the T protein forms 5,10-methylenetetrahydrofolate and ammonium, and the shared L protein reoxidizes the reduced lipoyl arm with NAD+. H-protein lipoylation, glycine-generating pathways, and downstream one-carbon metabolism are separate modules.

MODULE:glycine_cleavage_systemDRAFTCONCRETEProtein Complexmodules/glycine_cleavage_system.yaml
glycine decarboxylation via glycine cleavage systemGO:0019464
GO:0019464
glycine decarboxylation via glycine cleavage system
Defines the complete glycine-cleavage process represented by the module.
GO:0005960
glycine cleavage complex
Defines the P/H/T/L multienzyme assembly.
RHEA:24304
glycine dehydrogenase (decarboxylating) reaction
Defines transfer of the glycine-derived aminomethyl group to lipoyl-H protein.
RHEA:16945
aminomethyltransferase reaction
Defines transfer from aminomethyl-H protein to tetrahydrofolate.
RHEA:15045
dihydrolipoyl dehydrogenase reaction
Defines NAD+-dependent reoxidation of protein-bound dihydrolipoamide.
Reactome:R-HSA-6783984
Glycine degradation
The human pathway supplies reviewed eukaryotic implementations of the P, H, T, and L roles, including reactions R-HSA-5693967, R-HSA-5693977, and R-HSA-5694018.
file:human/GLDC/GLDC-ai-review.yaml
GLDC gene review (human)
The completed review grounds human GLDC as the P-protein representative.
file:human/GCSH/GCSH-ai-review.yaml
GCSH gene review (human)
The completed review grounds human GCSH as the lipoyl H-protein representative.
file:human/AMT/AMT-ai-review.yaml
AMT gene review (human)
The completed review grounds human AMT as the T-protein representative.
file:human/DLD/DLD-ai-review.yaml
DLD gene review (human)
The completed review grounds human DLD as the shared L-protein representative.
PMID:27303730
GcsR, a TyrR-Like Enhancer-Binding Protein, Regulates Expression of the Glycine Cleavage System in Pseudomonas aeruginosa PAO1.
Comparative Pseudomonas evidence establishes two GCS sets and a glycine-responsive gcs2 operon.
PMID:23457254
Gene PA2449 is essential for glycine metabolism and pyocyanin biosynthesis in Pseudomonas aeruginosa PAO1.
Comparative Pseudomonas genetics links GcsR to glycine assimilation and GCS-gene expression.
PANTHER:PTN000206531
PAINT glycine dehydrogenase ancestral node
The local PTHR11773 PAINT table assigns GO:0004375 and GO:0019464 to PTN000206531, with experimentally characterized UniProt proteins among its seeds.
PANTHER:PTN000354058
PAINT aminomethyltransferase ancestral node
The local PTHR43757 PAINT table assigns GO:0004047 to PTN000354058, with bacterial and eukaryotic aminomethyltransferases among its seeds.
file:projects/P_PUTIDA/deep-research/PSEPK__glycine_cleavage_system__ppu00260-deep-research-openscientist.md
OpenScientist PSEPK glycine cleavage system synthesis
Species-aware retrieval resolves two complete P/H/T sets in KT2440 and a shared, locus-ambiguous L-protein step with three plausible E3 candidates.

This replaces the former human disease-centric, one-part representation. The reusable module is not restricted to mitochondria and does not encode nonketotic hyperglycinemia. KT2440 has two P/H/T paralog sets: Q88P65/Q88P64/Q88P67 and Q88CI9/Q88CI8/Q88CI7. Its L step is satisfiable, but current evidence does not establish which of Q88FB1, Q88C17, or Q88EP9 is the physiological GCS E3; Q88FB1 is retained only as a provisional exemplar based on its exact enzyme annotation, not as a physiologically demonstrated or literature-ranked GCS partner. LipA/LipB activation, upstream betaine and sarcosine catabolism, and GlyA-mediated serine/glycine interconversion remain outside this boundary.

5Nodes
4Parts
0Variant Sets
0Variants
4Annotons
4Connections

Derived QC

Recommended-field compliance

55.6% recommended fields populated
  • module.knowledge_gaps[0] · status (0/1)
  • module.knowledge_gaps[0] · provenance (0/1)
  • module.knowledge_gaps[1] · status (0/1)
  • module.knowledge_gaps[1] · provenance (0/1)

Module deep research

✗ none found

No MODULE:glycine_cleavage_system 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.

Gene-review completeness (13/13 grounded genes reviewed)

11 complete review(s) · 4 with deep research · 0 missing review · 9 reviewed but lacking deep research

Gene Review Complete Deep research
AMT P48728 ✓ ✓ ✗
DLD P09622 ✓ ✓ ✓
GCSH P23434 ✓ ✓ ✗
gcvH1 Q88P64 ✓ 5/6 ✗
gcvH2 Q88CI8 ✓ 5/6 ✗
gcvP1 Q88P65 ✓ ✓ ✗
gcvP2 Q88CI9 ✓ ✓ ✗
gcvT Q88CI7 ✓ ✓ ✗
gcvT-I Q88P67 ✓ ✓ ✗
GLDC P23378 ✓ ✓ ✗
lpd Q88C17 ✓ ✓ ✓
lpdG Q88FB1 ✓ ✓ ✓
lpdV Q88EP9 ✓ ✓ ✓

Details

Glycine cleavage systemProtein Complexglycine_cleavage_system
glycine decarboxylation via glycine cleavage systemGO:0019464

Connections

gcvP_reaction -> gcvH_carrier Provides Input For
gcvH_carrier -> gcvT_reaction Provides Input For
gcvT_reaction -> gcvL_reaction Provides Input For
gcvL_reaction -> gcvP_reaction Provides Input For
Part 1: glycine decarboxylation and aminomethyl loading
P-protein glycine decarboxylationReactiongcvP_reaction

Annotons

Glycine cleavage P protein
gcvP_activity
Participant: Family: glycine dehydrogenase (decarboxylating) family
Family:
glycine dehydrogenase (decarboxylating) familyPANTHER:PTHR11773
Representative Members: PSEPK GcvP1UniProtKB:Q88P65 PSEPK GcvP2UniProtKB:Q88CI9 human GLDCUniProtKB:P23378
Required Function:
glycine dehydrogenase (decarboxylating) activityGO:0004375

Function

glycine dehydrogenase (decarboxylating) activityGO:0004375
Substrates: glycine lipoyl-H protein
Products: carbon dioxide aminomethyl-dihydrolipoyl-H protein

Processes

glycine decarboxylation via glycine cleavage systemGO:0019464

PLP-dependent loading of the glycine-derived aminomethyl group onto H protein.

Part 2: lipoyl-arm intermediate relay
H-protein lipoyl carrierModulegcvH_carrier

Annotons

Glycine cleavage H protein
gcvH_carrier_activity
Participant: Family: glycine cleavage H-protein family
Family:
glycine cleavage H-protein familyPANTHER:PTHR11715
Representative Members: PSEPK GcvH1UniProtKB:Q88P64 PSEPK GcvH2UniProtKB:Q88CI8 human GCSHUniProtKB:P23434
Required Function:
lipoic acid bindingGO:0031405

Function

lipoic acid bindingGO:0031405

Processes

glycine decarboxylation via glycine cleavage systemGO:0019464

Non-catalytic swinging arm that carries intermediates between P, T, and L proteins.

Part 3: one-carbon transfer to tetrahydrofolate
T-protein aminomethyl transferReactiongcvT_reaction

Annotons

Glycine cleavage T protein
gcvT_activity
Participant: Family: aminomethyltransferase family
Family:
aminomethyltransferase familyPANTHER:PTHR43757
Representative Members: PSEPK GcvT-IUniProtKB:Q88P67 PSEPK GcvTUniProtKB:Q88CI7 human AMTUniProtKB:P48728
Required Function:
aminomethyltransferase activityGO:0004047

Function

aminomethyltransferase activityGO:0004047
Substrates: aminomethyl-dihydrolipoyl-H protein tetrahydrofolate
Products: dihydrolipoyl-H protein 5,10-methylenetetrahydrofolate ammonium

Processes

glycine decarboxylation via glycine cleavage systemGO:0019464

Releases ammonium and transfers the one-carbon unit to tetrahydrofolate.

Part 4: lipoyl-carrier reoxidation
L-protein dihydrolipoyl dehydrogenase reactionReactiongcvL_reaction

Annotons

Shared glycine-cleavage L protein
gcvL_activity
Participant: Family: class-I pyridine nucleotide-disulfide oxidoreductase family
Family:
class-I pyridine nucleotide-disulfide oxidoreductase familyPANTHER:PTHR22912
Representative Members: PSEPK LpdGUniProtKB:Q88FB1 PSEPK LpdUniProtKB:Q88C17 PSEPK LpdVUniProtKB:Q88EP9 human DLDUniProtKB:P09622
Required Function:
dihydrolipoyl dehydrogenase (NADH) activityGO:0004148

Function

dihydrolipoyl dehydrogenase (NADH) activityGO:0004148
Substrates: dihydrolipoyl-H protein NAD+
Products: lipoyl-H protein NADH proton

Processes

glycine decarboxylation via glycine cleavage systemGO:0019464

Shared FAD enzyme that regenerates oxidized lipoyl-H protein.