L-lysine biosynthesis IV
gomodel:YeastPathways_LYSINE-AMINOAD-PWY-2
L-lysine biosynthesis IV in Saccharomyces cerevisiae S288C routes acetyl-CoA and 2-oxoglutarate through homocitrate, homoaconitate, 2-oxoadipate, 2-aminoadipate, saccharopine, and L-2-aminoadipate 6-semialdehyde chemistry to L-lysine. Homocitrate dehydration is assigned to ACO2 with a minor ACO1 contribution; LYS4 catalyzes the following homoaconitate hydration.
- Pathway type
- amino acid biosynthesis
- Organism scope
Pathway network
48 nodes · 89 asserted directed edges
Arrows show recorded subject → object relationships, not necessarily metabolic flow. Select a node for details or an arrow for evidence. Scroll, zoom or find a node to explore.
- Reaction / activity
- Chemical / cofactor
- Protein / complex
- Cell / process context
- Solid arrow: mechanistic relation
- Dashed arrow: membership, location or cofactor relation
Components and activities
| Node | Kind or role | Source direction |
|---|---|---|
Saccharomyces cerevisiae S288CNCBITaxon:559292 | taxon | |
coenzyme A(4-)CHEBI:57287 | small molecule | |
2-oxoadipate(2-)CHEBI:57499 | small molecule | |
(-)-homoisocitrate(3-)CHEBI:15404 | small molecule | |
but-1-ene-1,2,4-tricarboxylateCHEBI:58174 | small molecule | |
2-oxoglutarate(2-)CHEBI:16810 | small molecule | |
waterCHEBI:15377 | small molecule | |
LYS4 ScerSGD:S000002642 | protein | |
acetyl-CoA(4-)CHEBI:57288 | small molecule | |
L-2-aminoadipate(1-)CHEBI:58672 | small molecule | |
L-saccharopinate(1-)CHEBI:57951 | small molecule | |
cytosolGO:0005829 | cellular component | |
L-lysine biosynthetic processGO:0009085 | biological process | |
L-glutamate(1-)CHEBI:29985 | small molecule | |
carbon dioxideCHEBI:16526 | small molecule | |
(2R)-homocitrate(3-)CHEBI:58884 | small molecule | |
L-allysine zwitterionCHEBI:58321 | small molecule | |
hydronCHEBI:15378 | small molecule | |
NADH(2-)CHEBI:57945 | small molecule | |
NAD(1-)CHEBI:57540 | small molecule | |
LYS12 ScerSGD:S000001356 | protein | |
NADPH(4-)CHEBI:57783 | small molecule | |
NADP(3-)CHEBI:58349 | small molecule | |
LYS1 ScerSGD:S000001473 | protein | |
LYS21 ScerSGD:S000002289 | protein | |
LYS9 ScerSGD:S000005333 | protein | |
LYS2 ScerSGD:S000000319 | protein | |
LYS20 ScerSGD:S000002341 | protein | |
L-lysinium(1+)CHEBI:32551 | small molecule | |
ARO8 ScerSGD:S000003170 | protein | |
mitochondrionGO:0005739 | cellular component | |
peroxisomeGO:0005777 | cellular component | |
cytoplasmGO:0005737 | cellular component | |
ACO2 ScerSGD:S000003736 | protein | |
ACO1 ScerSGD:S000004295 | protein | |
tetra-mu3-sulfido-tetraironCHEBI:49883 | cofactor | |
magnesium(2+)CHEBI:18420 | cofactor | |
manganese(2+)CHEBI:29035 | cofactor | |
pantetheine 4'-phosphate(2-)CHEBI:47942 | cofactor | |
pyridoxal 5'-phosphate(2-)CHEBI:597326 | cofactor | |
saccharopine dehydrogenase (NAD+, L-lysine-forming) activitygomodel:1.5.1.7-RXN | molecular activity | |
L-2-aminoadipate:2-oxoglutarate transaminase activitygomodel:2-AMINOADIPATE-AMINOTRANSFERASE-RXN | molecular activity | |
homoaconitate hydratase activitygomodel:HOMOACONITATE-HYDRATASE-RXN | molecular activity | |
homocitrate synthase activitygomodel:HOMOCITRATE-SYNTHASE-RXN | molecular activity | |
homoisocitrate dehydrogenase activitygomodel:RXN-7970 | molecular activity | |
saccharopine dehydrogenase (NADP+, L-glutamate-forming) activitygomodel:RXN3O-127 | molecular activity | |
homocitrate dehydratase activitygomodel:RXN3O-1983 | molecular activity | |
L-aminoadipate-semialdehyde dehydrogenase [NAD(P)+] activitygomodel:RXN3O-9808 | molecular activity | |
homocitrate synthase activitygomodel:YeastPathways_LYSINE-AMINOAD-PWY-2/6a4c244800001076 | molecular activity |
Mechanistic edges
| Subject | Predicate and description | Object | Evidence |
|---|---|---|---|
homocitrate synthase activitygomodel:HOMOCITRATE-SYNTHASE-RXN | has_output | coenzyme A(4-)CHEBI:57287 |
|
L-2-aminoadipate:2-oxoglutarate transaminase activitygomodel:2-AMINOADIPATE-AMINOTRANSFERASE-RXN | has_input | 2-oxoadipate(2-)CHEBI:57499 |
|
homoaconitate hydratase activitygomodel:HOMOACONITATE-HYDRATASE-RXN | has_output | (-)-homoisocitrate(3-)CHEBI:15404 |
|
homocitrate synthase activitygomodel:YeastPathways_LYSINE-AMINOAD-PWY-2/6a4c244800001076 | has_output | coenzyme A(4-)CHEBI:57287 |
|
homocitrate dehydratase activitygomodel:RXN3O-1983 | has_output | but-1-ene-1,2,4-tricarboxylateCHEBI:58174 |
|
L-2-aminoadipate:2-oxoglutarate transaminase activitygomodel:2-AMINOADIPATE-AMINOTRANSFERASE-RXN | has_output | 2-oxoglutarate(2-)CHEBI:16810 |
|
L-aminoadipate-semialdehyde dehydrogenase [NAD(P)+] activitygomodel:RXN3O-9808 | has_output | waterCHEBI:15377 |
|
homocitrate synthase activitygomodel:HOMOCITRATE-SYNTHASE-RXN | has_input | 2-oxoglutarate(2-)CHEBI:16810 |
|
homocitrate synthase activitygomodel:HOMOCITRATE-SYNTHASE-RXN | has_input | acetyl-CoA(4-)CHEBI:57288 |
|
homocitrate synthase activitygomodel:HOMOCITRATE-SYNTHASE-RXN | has_input | waterCHEBI:15377 |
|
L-aminoadipate-semialdehyde dehydrogenase [NAD(P)+] activitygomodel:RXN3O-9808 | has_input | L-2-aminoadipate(1-)CHEBI:58672 |
|
saccharopine dehydrogenase (NADP+, L-glutamate-forming) activitygomodel:RXN3O-127 | has_output | waterCHEBI:15377 |
|
saccharopine dehydrogenase (NAD+, L-lysine-forming) activitygomodel:1.5.1.7-RXN | has_input | L-saccharopinate(1-)CHEBI:57951 |
|
saccharopine dehydrogenase (NADP+, L-glutamate-forming) activitygomodel:RXN3O-127 | has_output | L-saccharopinate(1-)CHEBI:57951 |
|
homocitrate synthase activitygomodel:HOMOCITRATE-SYNTHASE-RXN | part_of | L-lysine biosynthetic processGO:0009085 |
|
saccharopine dehydrogenase (NADP+, L-glutamate-forming) activitygomodel:RXN3O-127 | has_input | L-glutamate(1-)CHEBI:29985 |
|
homoisocitrate dehydrogenase activitygomodel:RXN-7970 | has_output | carbon dioxideCHEBI:16526 |
|
homocitrate synthase activitygomodel:HOMOCITRATE-SYNTHASE-RXN | has_output | (2R)-homocitrate(3-)CHEBI:58884 |
|
L-aminoadipate-semialdehyde dehydrogenase [NAD(P)+] activitygomodel:RXN3O-9808 | has_output | L-allysine zwitterionCHEBI:58321 |
|
saccharopine dehydrogenase (NAD+, L-lysine-forming) activitygomodel:1.5.1.7-RXN | has_output | hydronCHEBI:15378 |
|
homoisocitrate dehydrogenase activitygomodel:RXN-7970 | has_output | NADH(2-)CHEBI:57945 |
|
L-2-aminoadipate:2-oxoglutarate transaminase activitygomodel:2-AMINOADIPATE-AMINOTRANSFERASE-RXN | occurs_in | cytosolGO:0005829 |
|
LYS4 ScerSGD:S000002642 | enables | homoaconitate hydratase activitygomodel:HOMOACONITATE-HYDRATASE-RXN |
|
homoisocitrate dehydrogenase activitygomodel:RXN-7970 | has_input | NAD(1-)CHEBI:57540 |
|
homocitrate synthase activitygomodel:YeastPathways_LYSINE-AMINOAD-PWY-2/6a4c244800001076 | has_input | 2-oxoglutarate(2-)CHEBI:16810 |
|
LYS12 ScerSGD:S000001356 | enables | homoisocitrate dehydrogenase activitygomodel:RXN-7970 |
|
homocitrate synthase activitygomodel:YeastPathways_LYSINE-AMINOAD-PWY-2/6a4c244800001076 | has_output | (2R)-homocitrate(3-)CHEBI:58884 |
|
homocitrate dehydratase activitygomodel:RXN3O-1983 | has_output | waterCHEBI:15377 |
|
L-aminoadipate-semialdehyde dehydrogenase [NAD(P)+] activitygomodel:RXN3O-9808 | has_input | NADPH(4-)CHEBI:57783 |
|
L-aminoadipate-semialdehyde dehydrogenase [NAD(P)+] activitygomodel:RXN3O-9808 | part_of | L-lysine biosynthetic processGO:0009085 |
|
homoisocitrate dehydrogenase activitygomodel:RXN-7970 | part_of | L-lysine biosynthetic processGO:0009085 |
|
saccharopine dehydrogenase (NAD+, L-lysine-forming) activitygomodel:1.5.1.7-RXN | part_of | L-lysine biosynthetic processGO:0009085 |
|
L-2-aminoadipate:2-oxoglutarate transaminase activitygomodel:2-AMINOADIPATE-AMINOTRANSFERASE-RXN | has_output | L-2-aminoadipate(1-)CHEBI:58672 |
|
saccharopine dehydrogenase (NADP+, L-glutamate-forming) activitygomodel:RXN3O-127 | part_of | L-lysine biosynthetic processGO:0009085 |
|
L-aminoadipate-semialdehyde dehydrogenase [NAD(P)+] activitygomodel:RXN3O-9808 | has_output | NADP(3-)CHEBI:58349 |
|
homocitrate synthase activitygomodel:HOMOCITRATE-SYNTHASE-RXN | occurs_in | cytosolGO:0005829 |
|
homocitrate synthase activitygomodel:YeastPathways_LYSINE-AMINOAD-PWY-2/6a4c244800001076 | has_input | waterCHEBI:15377 |
|
saccharopine dehydrogenase (NADP+, L-glutamate-forming) activitygomodel:RXN3O-127 | has_input | hydronCHEBI:15378 |
|
homocitrate synthase activitygomodel:YeastPathways_LYSINE-AMINOAD-PWY-2/6a4c244800001076 | part_of | L-lysine biosynthetic processGO:0009085 |
|
homocitrate synthase activitygomodel:YeastPathways_LYSINE-AMINOAD-PWY-2/6a4c244800001076 | has_output | hydronCHEBI:15378 |
|
LYS1 ScerSGD:S000001473 | enables | saccharopine dehydrogenase (NAD+, L-lysine-forming) activitygomodel:1.5.1.7-RXN |
|
homoaconitate hydratase activitygomodel:HOMOACONITATE-HYDRATASE-RXN | part_of | L-lysine biosynthetic processGO:0009085 |
|
saccharopine dehydrogenase (NADP+, L-glutamate-forming) activitygomodel:RXN3O-127 | occurs_in | cytosolGO:0005829 |
|
L-2-aminoadipate:2-oxoglutarate transaminase activitygomodel:2-AMINOADIPATE-AMINOTRANSFERASE-RXN | has_input | L-glutamate(1-)CHEBI:29985 |
|
saccharopine dehydrogenase (NADP+, L-glutamate-forming) activitygomodel:RXN3O-127 | has_input | L-allysine zwitterionCHEBI:58321 |
|
homoisocitrate dehydrogenase activitygomodel:RXN-7970 | has_output | 2-oxoadipate(2-)CHEBI:57499 |
|
LYS21 ScerSGD:S000002289 | enables | homocitrate synthase activitygomodel:YeastPathways_LYSINE-AMINOAD-PWY-2/6a4c244800001076 |
|
homoisocitrate dehydrogenase activitygomodel:RXN-7970 | has_input | (-)-homoisocitrate(3-)CHEBI:15404 |
|
saccharopine dehydrogenase (NAD+, L-lysine-forming) activitygomodel:1.5.1.7-RXN | has_output | 2-oxoglutarate(2-)CHEBI:16810 |
|
L-2-aminoadipate:2-oxoglutarate transaminase activitygomodel:2-AMINOADIPATE-AMINOTRANSFERASE-RXN | part_of | L-lysine biosynthetic processGO:0009085 |
|
L-aminoadipate-semialdehyde dehydrogenase [NAD(P)+] activitygomodel:RXN3O-9808 | has_input | hydronCHEBI:15378 |
|
saccharopine dehydrogenase (NADP+, L-glutamate-forming) activitygomodel:RXN3O-127 | has_output | NADP(3-)CHEBI:58349 |
|
LYS9 ScerSGD:S000005333 | enables | saccharopine dehydrogenase (NADP+, L-glutamate-forming) activitygomodel:RXN3O-127 |
|
homocitrate synthase activitygomodel:YeastPathways_LYSINE-AMINOAD-PWY-2/6a4c244800001076 | has_input | acetyl-CoA(4-)CHEBI:57288 |
|
LYS2 ScerSGD:S000000319 | enables | L-aminoadipate-semialdehyde dehydrogenase [NAD(P)+] activitygomodel:RXN3O-9808 |
|
LYS20 ScerSGD:S000002341 | enables | homocitrate synthase activitygomodel:HOMOCITRATE-SYNTHASE-RXN |
|
saccharopine dehydrogenase (NAD+, L-lysine-forming) activitygomodel:1.5.1.7-RXN | has_output | L-lysinium(1+)CHEBI:32551 |
|
saccharopine dehydrogenase (NADP+, L-glutamate-forming) activitygomodel:RXN3O-127 | has_input | NADPH(4-)CHEBI:57783 |
|
homocitrate synthase activitygomodel:HOMOCITRATE-SYNTHASE-RXN | has_output | hydronCHEBI:15378 |
|
homoaconitate hydratase activitygomodel:HOMOACONITATE-HYDRATASE-RXN | has_input | waterCHEBI:15377 |
|
ARO8 ScerSGD:S000003170 | enables | L-2-aminoadipate:2-oxoglutarate transaminase activitygomodel:2-AMINOADIPATE-AMINOTRANSFERASE-RXN |
|
homocitrate dehydratase activitygomodel:RXN3O-1983 | part_of | L-lysine biosynthetic processGO:0009085 |
|
L-aminoadipate-semialdehyde dehydrogenase [NAD(P)+] activitygomodel:RXN3O-9808 | occurs_in | cytosolGO:0005829 |
|
homocitrate dehydratase activitygomodel:RXN3O-1983 | has_input | (2R)-homocitrate(3-)CHEBI:58884 |
|
saccharopine dehydrogenase (NAD+, L-lysine-forming) activitygomodel:1.5.1.7-RXN | has_output | NADH(2-)CHEBI:57945 |
|
saccharopine dehydrogenase (NAD+, L-lysine-forming) activitygomodel:1.5.1.7-RXN | has_input | waterCHEBI:15377 |
|
homoaconitate hydratase activitygomodel:HOMOACONITATE-HYDRATASE-RXN | has_input | but-1-ene-1,2,4-tricarboxylateCHEBI:58174 |
|
saccharopine dehydrogenase (NAD+, L-lysine-forming) activitygomodel:1.5.1.7-RXN | has_input | NAD(1-)CHEBI:57540 |
|
LYS4 ScerSGD:S000002642 | located_in Physical protein location from reviewed UniProt. ECO:0000269 (PubMed:14562095) | mitochondrionGO:0005739 |
|
LYS12 ScerSGD:S000001356 | located_in Physical protein location from reviewed UniProt. ECO:0000269 (PubMed:14562095); ECO:0000269 (PubMed:14576278) | mitochondrionGO:0005739 |
|
LYS1 ScerSGD:S000001473 | located_in Physical protein location from reviewed UniProt. ECO:0000269 (PubMed:26928762); ECO:0000269 (PubMed:28928432) | peroxisomeGO:0005777 |
|
LYS21 ScerSGD:S000002289 | located_in Physical protein location from reviewed UniProt. ECO:0000305 | mitochondrionGO:0005739 |
|
LYS20 ScerSGD:S000002341 | located_in Physical protein location from reviewed UniProt. evidence code not specified by source | cytoplasmGO:0005737 |
|
ARO8 ScerSGD:S000003170 | located_in Physical protein location from reviewed UniProt. ECO:0000269 (PubMed:14562095) | cytoplasmGO:0005737 |
|
ACO2 ScerSGD:S000003736 | enables PMID:23106124 separates homocitrate dehydration (ACO2, with minor ACO1 contribution) from homoaconitate hydration (LYS4). | homocitrate dehydratase activitygomodel:RXN3O-1983 |
|
ACO2 ScerSGD:S000003736 | located_in Physical protein location; does not place every activity of this enzyme in this compartment. ACO1 is mainly mitochondrial. | mitochondrionGO:0005739 |
|
ACO1 ScerSGD:S000004295 | enables PMID:23106124 separates homocitrate dehydration (ACO2, with minor ACO1 contribution) from homoaconitate hydration (LYS4). | homocitrate dehydratase activitygomodel:RXN3O-1983 |
|
ACO1 ScerSGD:S000004295 | located_in Physical protein location; does not place every activity of this enzyme in this compartment. ACO1 is mainly mitochondrial. | mitochondrionGO:0005739 |
|
ACO1 ScerSGD:S000004295 | located_in Physical protein location; does not place every activity of this enzyme in this compartment. ACO1 is mainly mitochondrial. | cytoplasmGO:0005737 |
|
LYS4 ScerSGD:S000002642 | has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. UniProt evidence: ECO:0000250 Binds 1 [4Fe-4S] cluster per subunit. UniProt note evidence: ECO:0000250 | tetra-mu3-sulfido-tetraironCHEBI:49883 |
|
LYS12 ScerSGD:S000001356 | has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. UniProt evidence: ECO:0000269 (PubMed:17223711); ECO:0000269 (PubMed:19530703) Binds 1 Mg(2+) ion per subunit. UniProt note evidence: ECO:0000269 (PubMed:17223711); ECO:0000269 (PubMed:19530703) | magnesium(2+)CHEBI:18420 |
|
LYS21 ScerSGD:S000002289 | has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. UniProt evidence: ECO:0000250 (UniProtKB:O87198) | magnesium(2+)CHEBI:18420 |
|
LYS21 ScerSGD:S000002289 | has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. UniProt evidence: ECO:0000250 (UniProtKB:O87198) | manganese(2+)CHEBI:29035 |
|
LYS2 ScerSGD:S000000319 | has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. Reviewed source qualification: The source describes a covalently attached cofactor moiety. Keep that bound-state qualification; no free cosubstrate consumption is inferred. UniProt evidence: ECO:0000269 (PubMed:10320345) Binds 1 phosphopantetheine covalently. UniProt note evidence: ECO:0000269 (PubMed:10320345) | pantetheine 4'-phosphate(2-)CHEBI:47942 |
|
LYS20 ScerSGD:S000002341 | has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. UniProt evidence: ECO:0000250 (UniProtKB:O87198) | magnesium(2+)CHEBI:18420 |
|
LYS20 ScerSGD:S000002341 | has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. UniProt evidence: ECO:0000250 (UniProtKB:O87198) | manganese(2+)CHEBI:29035 |
|
ARO8 ScerSGD:S000003170 | has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. UniProt evidence: ECO:0000269 (PubMed:23893908) | pyridoxal 5'-phosphate(2-)CHEBI:597326 |
|
ACO2 ScerSGD:S000003736 | has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. UniProt evidence: ECO:0000250 (UniProtKB:P20004) Binds 1 [4Fe-4S] cluster per subunit. UniProt note evidence: ECO:0000250 (UniProtKB:P20004) | tetra-mu3-sulfido-tetraironCHEBI:49883 |
|
ACO1 ScerSGD:S000004295 | has_cofactor UniProtKB reviewed (Swiss-Prot) annotation. UniProt evidence: ECO:0000269 (PubMed:27738674) Binds 1 [4Fe-4S] cluster per subunit. UniProt note evidence: ECO:0000250 (UniProtKB:P20004) | tetra-mu3-sulfido-tetraironCHEBI:49883 |
|
References
gomodel:YeastPathways_LYSINE-AMINOAD-PWY-2SGD GO-CAM L-lysine biosynthesis IV model (source version: Pinned Noctua JSON archive; model date 2026-07-10; member ./YeastPathways_LYSINE-AMINOAD-PWY-2.json)UniProtKB:P49367Reviewed UniProtKB P49367 location annotations (source version: UniProt release 2026_03)UniProtKB:P40495Reviewed UniProtKB P40495 location annotations (source version: UniProt release 2026_03)UniProtKB:P38998Reviewed UniProtKB P38998 location annotations (source version: UniProt release 2026_03)UniProtKB:Q12122Reviewed UniProtKB Q12122 location annotations (source version: UniProt release 2026_03)UniProtKB:P48570Reviewed UniProtKB P48570 location annotations (source version: UniProt release 2026_03)UniProtKB:P53090Reviewed UniProtKB P53090 location annotations (source version: UniProt release 2026_03)UniProtKB:P39533Reviewed UniProt P39533: catalytic-function assertions (source version: 2026_03)UniProtKB:P19414Reviewed UniProt P19414: catalytic-function assertions (source version: 2026_03)UniProtKB:P07702UniProtKB P07702 cofactor annotations (source version: 2026_03)
Curation history
- Codex; review-causal-graph; Reviewed every native GO-CAM fact; preserved precise input/output, causal, location, membership and complex-part relations with traceable structured source evidence. Kept distinct generic physical instances and recorded source-scope exclusions in the cohort review ledger.
- Codex
- EDIT — Audit causal activity compartments and preserve scoped protein location evidence
Reviewed all 9 activity location assignments and 8 mapped physical proteins against reviewed S288C UniProt release2026_03 location/function/caution batch SHA256 95f72dcc644358c480e0e59f996cf88533558b5fa4256460a030e0a1eaf9678d. Added 6 independently supported location edges and quarantined 5 generic cytosol source assertions. Mapped physical protein locations via exact SGD cross-references; retained source ECO grades, molecular form and conditional notes. Physical protein location alone never generates activity location. Explicitly inspected functional assertions support bounded activity projections. Every original activity location and exclusion is recorded in reports/causal_graph_review/gocam-location-review.json. No independent location annotation is treated as an evidence gap, not a negative result. Cytoplasm is not narrowed to cytosol. Microsome fractions are not projected as in-vivo organelles. Semantic validation passed all85 records;4 independent source-role acceptance tests passed.
- EDIT — Audit causal activity compartments and preserve scoped protein location evidence
- claude-code
- EDIT — Correct homocitrate dehydration enzyme assignment
Inspected complete primary paper PMID23106124 and exact current UniProt functions. Replaced LYS4 homocitrate-dehydration assignment with ACO2 and explicitly minor ACO1 contribution; retained LYS4 homoaconitate hydration and added independently annotated physical compartments. Source conflict ledger: reports/causal_graph_review/gocam-assignment-conflicts.json. Schema validation and idempotent dry-run passed.
- EDIT — Correct homocitrate dehydration enzyme assignment