L-valine, L-leucine, and L-isoleucine biosynthesis

De novo biosynthesis of the three branched-chain amino acids in bacteria, archaea, fungi and plants; the pathway is absent from animals. L-isoleucine synthesis begins with threonine deamination to 2-oxobutanoate. An acetohydroxy-acid synthase (a catalytic large subunit with a regulatory small subunit), ketol-acid reductoisomerase and dihydroxy-acid dehydratase then form a shared catalytic trunk that processes either the valine precursor derived from two pyruvate molecules or the isoleucine precursor derived from pyruvate plus 2-oxobutanoate. The valine intermediate 2-oxoisovalerate also enters a three-reaction leucine extension (2-isopropylmalate synthase, isopropylmalate isomerase and 3-isopropylmalate dehydrogenase). A branched-chain amino-acid aminotransferase performs the terminal transamination for all three products. The reaction chain is conserved, but two features vary by lineage. First, isopropylmalate isomerase is a heteromeric LeuC-LeuD enzyme in bacteria and plants but a single fused polypeptide in fungi. Second, in fungi the pathway is split between compartments: threonine deaminase, the shared trunk, most 2-isopropylmalate synthase and a biosynthetic aminotransferase are in the mitochondrial matrix, 2-isopropylmalate is exported to the cytosol by a mitochondrial carrier, and the isomerase and dehydrogenase are cytosolic. In budding yeast, mitochondrial BAT1 and cytosolic BAT2 are paralogous aminotransferases, with BAT1 favoured for biosynthesis and BAT2 for catabolism.

MODULE:branched_chain_amino_acid_biosynthesisDRAFTMetabolic Pathwaymodules/branched_chain_amino_acid_biosynthesis.yaml

branched-chain amino acid biosynthetic processGO:0009082 L-valine biosynthetic processGO:0009099 L-isoleucine biosynthetic processGO:1901705 L-leucine biosynthetic processGO:0009098

GO:0009082

Branched-chain amino acid biosynthetic process

The module is grounded in the GO biological process for valine, leucine, and isoleucine biosynthesis.

GO:0009099

L-valine biosynthetic process

Product-specific child process covered by the shared trunk plus terminal transamination.

GO:1901705

L-isoleucine biosynthetic process

Product-specific child process covered by threonine deamination, the shared trunk and terminal transamination.

GO:0009098

L-leucine biosynthetic process

Product-specific child process covered by the shared trunk, the leucine extension and terminal transamination.

YeastPathways:BRANCHED-CHAIN-AA-SYN-PWY-1

superpathway of branched chain amino acid biosynthesis (S. cerevisiae, SGD YeastPathways)

The SGD superpathway lists ILV1, ILV2/ILV6, ILV5, ILV3, LEU4/LEU9, LEU1 and BAT1/BAT2 as catalysts and gives no gene for the 3-isopropylmalate dehydrogenase reaction (RXN-13158). LEU2 was added for that step (it is present as the enabler of RXN-13158 in the SGD GO-CAM conversion), and OAC1 was added as the fungal 2-isopropylmalate exporter. The YeastPathways comment correctly describes the mitochondrial trunk, alpha-IPM export and cytosolic leucine branch.

YeastPathways:ILEUSYN-PWY-1

L-isoleucine biosynthesis I (from threonine) (S. cerevisiae, SGD YeastPathways)

Isoleucine sub-pathway (ILV1, ILV2/ILV6, ILV5, ILV3, BAT1/BAT2); every reaction is contained in this module.

YeastPathways:VALSYN-PWY

L-valine biosynthesis (S. cerevisiae, SGD YeastPathways)

Valine sub-pathway (ILV2/ILV6, ILV5, ILV3, BAT1/BAT2); every reaction is contained in this module.

YeastPathways:LEUSYN-PWY-1

L-leucine biosynthesis (S. cerevisiae, SGD YeastPathways)

Leucine-specific sub-pathway (LEU4/LEU9, LEU1, BAT1/BAT2); the 3-isopropylmalate dehydrogenase reaction is listed without a gene and is assigned here to LEU2.

PMID:12626680

Leucine biosynthesis in fungi: entering metabolism through the back door.

Review (cited by YeastPathways) describing the S. cerevisiae pathway and its compartmentation: the enzymes converting pyruvate and 2-oxobutanoate to the valine and isoleucine 2-oxoacid precursors and to alpha-isopropylmalate are largely mitochondrial, whereas isopropylmalate isomerase (LEU1) and beta-isopropylmalate dehydrogenase (LEU2) are entirely cytoplasmic; Bat1p is the mitochondrial and Bat2p the cytosolic branched-chain aminotransferase.

PMID:3289762

Regulation of isoleucine-valine biosynthesis in Saccharomyces cerevisiae.

Cited by YeastPathways for the isoleucine and valine sub-pathways.

PMID:22419079

Regulation of amino acid, nucleotide, and phosphate metabolism in Saccharomyces cerevisiae.

YeastBook review cited by YeastPathways for the superpathway and its regulation.

PMID:25408465

Inhibitors of amino acids biosynthesis as antifungal agents.

Cited by YeastPathways; background on the absence of the pathway from mammals and its use as an antifungal target.

PMID:37455545

Branched-chain amino acid biosynthesis in fungi.

Review of fungal BCAA biosynthesis noting that the pathway is well-characterized in S. cerevisiae and that gene duplication and functional divergence of pathway genes vary among fungi.

PMID:10213630

Expression, purification, characterization, and reconstitution of the large and small subunits of yeast acetohydroxyacid synthase.

ILV6 is a mitochondrial AHAS small subunit that stimulates ILV2 catalytic activity up to 7-fold and confers valine sensitivity.

PMID:3275644

Yeast LEU4 encodes mitochondrial and nonmitochondrial forms of alpha-isopropylmalate synthase.

LEU4 produces a long mitochondrial form and a short cytoplasmic form of alpha-isopropylmalate synthase; the short form is functional in leucine biosynthesis.

PMID:25841022

Diversification of Paralogous α-Isopropylmalate Synthases by Modulation of Feedback Control and Hetero-Oligomerization in Saccharomyces cerevisiae.

LEU4 and LEU9 encode alpha-IPM synthase isozymes; the Leu4 homodimer is leucine-sensitive, the Leu9 homodimer is resistant, and Leu4-Leu9 heterodimers form in vivo.

PMID:20657649

Two origins for the gene encoding alpha-isopropylmalate synthase in fungi.

S. pombe leu3+ encodes alpha-isopropylmalate synthase (its auxotrophy was complemented by Phycomyces leuA); the zygomycete/chytrid leuA genes are more closely related to plant and photosynthetic-bacterial homologs than to ascomycete or basidiomycete genes, so fungi have two origins for this enzyme.

PMID:18682385

alpha-Isopropylmalate, a leucine biosynthesis intermediate in yeast, is transported by the mitochondrial oxalacetate carrier.

Alpha-IPM produced in mitochondria must be exported to the cytosol; the reconstituted mitochondrial oxalacetate carrier Oac1p transports alpha-IPM, and an oac1 leu4 double deletion cannot grow on fermentable substrates without leucine.

PMID:8798704

Mitochondrial and cytosolic branched-chain amino acid transaminases from yeast, homologs of the myc oncogene-regulated Eca39 protein.

Bat1p is targeted to the mitochondrial matrix and Bat2p is cytosolic; the bat1 bat2 double deletion is auxotrophic for Ile, Leu and Val.

PMID:8702755

Two yeast homologs of ECA39, a target for c-Myc regulation, code for cytosolic and mitochondrial branched-chain amino acid aminotransferases.

Independent identification of the cytosolic and mitochondrial yeast BCAT paralogs; cited by YeastPathways.

PMID:10989445

Branched-chain-amino-acid transaminases of yeast Saccharomyces cerevisiae.

Cited by YeastPathways for the BAT1/BAT2 transamination reactions.

PMID:21267457

Saccharomyces cerevisiae Bat1 and Bat2 aminotransferases have functionally diverged from the ancestral-like Kluyveromyces lactis orthologous enzyme.

The single K. lactis BCAT is bifunctional (biosynthesis and catabolism); in S. cerevisiae these roles are partitioned between BAT1 (biosynthetic, mitochondrial) and BAT2 (catabolic, cytosolic).

PMID:35325114

Response to leucine in Schizosaccharomyces pombe (fission yeast).

Review of the S. pombe pathway with experimental confirmation that SPAC17G8.06c (ilv3+) encodes dihydroxy-acid dehydratase (complemented by S. cerevisiae ILV3); leu3+ encodes the only known S. pombe 2-isopropylmalate synthase, leu2+ the isomerase, leu1+ the dehydrogenase and eca39+ the aminotransferase.

KEGG:ppu00290

Pseudomonas putida KT2440 valine, leucine, and isoleucine biosynthesis

The PSEPK pathway instance supplies the candidate set for the species-level satisfiability pass; map spillover and paralogous enzyme families require manual boundary curation.

file:projects/P_PUTIDA/data/psepk_gene_list.tsv

PSEPK UniProt metadata table

Supplies the exact PSEPK accessions, locus tags, protein families, and pathway keywords used for the representative members below.

file:projects/P_PUTIDA/deep-research/PSEPK__branched_chain_amino_acid_biosynthesis__ppu00290-deep-research-openscientist.md

OpenScientist module/pathway/taxon report for PSEPK branched-chain amino-acid biosynthesis

Supports the six-part pathway boundary, coverage by the selected KT2440 proteins, and exclusion of broad-map and catabolic-family candidates. Individual assignments remain based on exact database records and orthology because the report found no target-strain enzymology for the proteins themselves; IlvA and additional AHAS-family paralog roles remain unresolved.

PANTHER:PTN002459384

PAINT threonine-deaminase ancestral node

Local PTHR48078 PAINT data place GO:0004794 by IBD at PTN002459384, seeded in part by reviewed Escherichia coli IlvA P04968.

PANTHER:PTN000483120

PAINT ketol-acid reductoisomerase ancestral node

Local PTHR21371 PAINT data place GO:0004455 by IBD at PTN000483120, seeded in part by reviewed Escherichia coli IlvC P05793.

PANTHER:PTN002879868

PAINT isopropylmalate-dehydratase small-subunit ancestral node

Local PTHR43345 PAINT data place GO:0003861 by IBD at PTN002879868, seeded in part by reviewed Salmonella LeuD P04787.

PANTHER:PTN000216982

PAINT isopropylmalate-dehydrogenase ancestral node

Local PTHR42979 PAINT data place GO:0003862 by IBD at PTN000216982, seeded in part by reviewed Escherichia coli LeuB P30125.

13Nodes

10Parts

1Variant Sets

2Variants

12Annotons

10Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:branched_chain_amino_acid_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.

Reaction chaining (advisory)

✓ every PRECEDES step chains, or its break is acknowledged via chaining_status.

ilvIH_step → ilvC_step [NOT_CHECKED]
ilvC_step → ilvD_step [NOT_CHECKED]
ilvD_step → leucine_extension [NOT_CHECKED]
ilvD_step → ilvE_step [NOT_CHECKED]
leucine_extension → ilvE_step [NOT_CHECKED]

Function consistency and core coverage

31 gene-function check(s) reflected in core functions · 0 conflict(s) · 14 evidence or coverage gap(s) (60 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.

Annoton	Participant	Function	Assessment
ilvA_activity	ilvA-I (Pseudomonas putida KT2440) UniProtKB:Q88HB4 Family Representative	threonine deaminase activity GO:0004794	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvA_activity	ilvA-II (Pseudomonas putida KT2440) UniProtKB:Q88CN1 Family Representative	threonine deaminase activity GO:0004794	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvA_activity	ilvA (Escherichia coli K-12) UniProtKB:P04968 Family Representative	threonine deaminase activity GO:0004794	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ilvA_activity	ILV1 (Saccharomyces cerevisiae) UniProtKB:P00927 Family Representative	threonine deaminase activity GO:0004794	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvA_activity	tda1 (Schizosaccharomyces pombe) UniProtKB:O94634 Family Representative	threonine deaminase activity GO:0004794	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvI_activity	ilvI (Pseudomonas putida KT2440) UniProtKB:Q88DY8 Family Representative	acetolactate synthase activity GO:0003984	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvI_activity	ILV2 (Saccharomyces cerevisiae) UniProtKB:P07342 Family Representative	acetolactate synthase activity GO:0003984	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvI_activity	ilv1 (Schizosaccharomyces pombe) UniProtKB:P36620 Family Representative	acetolactate synthase activity GO:0003984	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvH_regulator_activity	ilvH (Pseudomonas putida KT2440) UniProtKB:Q88DY9 Family Representative	acetolactate synthase regulator activity GO:1990610	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvH_regulator_activity	ilvN (Escherichia coli K-12) UniProtKB:P0ADF8 Family Representative	acetolactate synthase regulator activity GO:1990610	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ilvH_regulator_activity	ILV6 (Saccharomyces cerevisiae) UniProtKB:P25605 Family Representative	acetolactate synthase regulator activity GO:1990610	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvH_regulator_activity	ilv6 (Schizosaccharomyces pombe) UniProtKB:O60086 Family Representative	acetolactate synthase regulator activity GO:1990610	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvC_activity	ilvC (Pseudomonas putida KT2440) UniProtKB:Q88DZ0 Family Representative	ketol-acid reductoisomerase activity GO:0004455	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvC_activity	ilvC (Escherichia coli K-12) UniProtKB:P05793 Family Representative	ketol-acid reductoisomerase activity GO:0004455	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ilvC_activity	ILV5 (Saccharomyces cerevisiae) UniProtKB:P06168 Family Representative	ketol-acid reductoisomerase activity GO:0004455	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvC_activity	ilv5 (Schizosaccharomyces pombe) UniProtKB:P78827 Family Representative	ketol-acid reductoisomerase activity GO:0004455	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvD_activity	ilvD (Pseudomonas putida KT2440) UniProtKB:Q88CQ2 Family Representative	dihydroxy-acid dehydratase activity GO:0004160	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvD_activity	ilvD (Escherichia coli K-12) UniProtKB:P05791 Family Representative	dihydroxy-acid dehydratase activity GO:0004160	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ilvD_activity	ILV3 (Saccharomyces cerevisiae) UniProtKB:P39522 Family Representative	dihydroxy-acid dehydratase activity GO:0004160	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvD_activity	ilv3 (Schizosaccharomyces pombe) UniProtKB:Q10318 Family Representative	dihydroxy-acid dehydratase activity GO:0004160	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
leuA_activity	leuA (Pseudomonas putida KT2440) UniProtKB:Q88P28 Family Representative	2-isopropylmalate synthase activity GO:0003852	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
leuA_activity	leuA (Corynebacterium glutamicum) UniProtKB:P42455 Family Representative	2-isopropylmalate synthase activity GO:0003852	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
leuA_activity	LEU4 (Saccharomyces cerevisiae) UniProtKB:P06208 Family Representative	2-isopropylmalate synthase activity GO:0003852	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
leuA_activity	LEU9 (Saccharomyces cerevisiae) UniProtKB:Q12166 Family Representative	2-isopropylmalate synthase activity GO:0003852	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
leuA_activity	leu3 (Schizosaccharomyces pombe) UniProtKB:O59736 Family Representative	2-isopropylmalate synthase activity GO:0003852	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
oac1_ipm_transport_activity	OAC1 (Saccharomyces cerevisiae) UniProtKB:P32332 Family Representative	isopropylmalate transmembrane transporter activity GO:0034658	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
oac1_ipm_transport_activity	oac1 (Schizosaccharomyces pombe) UniProtKB:Q9UTN1 Family Representative	isopropylmalate transmembrane transporter activity GO:0034658	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
leuC_activity	leuC (Pseudomonas putida KT2440) UniProtKB:Q88LE8 Family Representative	3-isopropylmalate dehydratase activity GO:0003861	Annotation Supported A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
leuC_activity	leuC (Escherichia coli K-12) UniProtKB:P0A6A6 Family Representative	3-isopropylmalate dehydratase activity GO:0003861	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
leuD_activity	leuD (Pseudomonas putida KT2440) UniProtKB:Q88LE7 Family Representative	3-isopropylmalate dehydratase activity GO:0003861	Annotation Supported A retained annotation or curated replacement supports this function, but core_functions does not yet reflect it.
leuD_activity	leuD (Salmonella typhimurium) UniProtKB:P04787 Family Representative	3-isopropylmalate dehydratase activity GO:0003861	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
leu1_fused_activity	LEU1 (Saccharomyces cerevisiae) UniProtKB:P07264 Family Representative	3-isopropylmalate dehydratase activity GO:0003861	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
leu1_fused_activity	leu2 (Schizosaccharomyces pombe) UniProtKB:O14289 Family Representative	3-isopropylmalate dehydratase activity GO:0003861	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
leuB_activity	leuB (Pseudomonas putida KT2440) UniProtKB:Q88LE5 Family Representative	3-isopropylmalate dehydrogenase activity GO:0003862	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
leuB_activity	leuB (Escherichia coli K-12) UniProtKB:P30125 Family Representative	3-isopropylmalate dehydrogenase activity GO:0003862	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
leuB_activity	LEU2 (Saccharomyces cerevisiae) UniProtKB:P04173 Family Representative	3-isopropylmalate dehydrogenase activity GO:0003862	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
leuB_activity	leu1 (Schizosaccharomyces pombe) UniProtKB:P18869 Family Representative	3-isopropylmalate dehydrogenase activity GO:0003862	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvE_activity	ilvE (Pseudomonas putida KT2440) UniProtKB:Q88H54 Family Representative	branched-chain-amino-acid:2-oxoglutarate transaminase activity GO:0004084	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvE_activity	ilvE (Escherichia coli K-12) UniProtKB:P0AB80 Family Representative	branched-chain-amino-acid:2-oxoglutarate transaminase activity GO:0004084	Review Missing No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
ilvE_activity	BAT1 (Saccharomyces cerevisiae) UniProtKB:P38891 Family Representative	branched-chain-amino-acid:2-oxoglutarate transaminase activity GO:0004084	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvE_activity	BAT2 (Saccharomyces cerevisiae) UniProtKB:P47176 Family Representative	branched-chain-amino-acid:2-oxoglutarate transaminase activity GO:0004084	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvE_activity	eca39 (Schizosaccharomyces pombe) UniProtKB:O14370 Family Representative	branched-chain-amino-acid:2-oxoglutarate transaminase activity GO:0004084	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ilvA_activity	full-length biosynthetic threonine deaminase family PANTHER:PTHR48078:SF11 Family	threonine deaminase activity GO:0004794	Family Supported Family review supports GO:0004794 for PANTHER:PTHR48078:SF11. Safe for the biosynthetic (SF11, SF10) and catabolic L-serine/L-threonine dehydratase subfamilies (SF2, SF8, SF16). It also holds for the TdcB members of SF6, but SF6 is not listed because it also contains ThrC threonine synthases. Not safe for DsdA (SF9). The safe boundary is the PAINT node PTN002459384, not any subfamily label. The module uses SF11 as its selector for this activity, which is correct.
ilvI_activity	biosynthetic acetohydroxy-acid synthase large subunit NCBIfam:TIGR00118 Family	acetolactate synthase activity GO:0003984	Family Review Missing No supported structured family review is available for NCBIfam:TIGR00118.
ilvH_regulator_activity	biosynthetic acetohydroxy-acid synthase small subunit PANTHER:PTHR30239:SF0 Family	acetolactate synthase regulator activity GO:1990610	Family Supported Family review supports GO:1990610 for PANTHER:PTHR30239:SF0. This is the module's term for the small-subunit role, and it holds for every characterized subfamily (SF0, SF4, SF18). It is not asserted for the uncharacterized ACT-domain subfamilies SF17, SF19 and SF27. No PAINT node in this family carries it.
ilvH_regulator_activity	biosynthetic acetohydroxy-acid synthase small subunit PANTHER:PTHR30239:SF4 Family	acetolactate synthase regulator activity GO:1990610	Family Supported Family review supports GO:1990610 for PANTHER:PTHR30239:SF4. This is the module's term for the small-subunit role, and it holds for every characterized subfamily (SF0, SF4, SF18). It is not asserted for the uncharacterized ACT-domain subfamilies SF17, SF19 and SF27. No PAINT node in this family carries it.
ilvH_regulator_activity	biosynthetic acetohydroxy-acid synthase small subunit PANTHER:PTHR30239:SF18 Family	acetolactate synthase regulator activity GO:1990610	Family Supported Family review supports GO:1990610 for PANTHER:PTHR30239:SF18. This is the module's term for the small-subunit role, and it holds for every characterized subfamily (SF0, SF4, SF18). It is not asserted for the uncharacterized ACT-domain subfamilies SF17, SF19 and SF27. No PAINT node in this family carries it.
ilvH_regulator_activity	biosynthetic acetohydroxy-acid synthase small subunit PANTHER:PTHR31242 Family	acetolactate synthase regulator activity GO:1990610	Family Supported Family review supports GO:1990610 FAMILY_WIDE. The module's term for the AHAS small-subunit annoton. All members are fungal ILV6 orthologs. PAINT asserts only the parent, enzyme regulator activity (GO:0030234).
ilvC_activity	type I ketol-acid reductoisomerase family PANTHER:PTHR21371:SF1 Family	ketol-acid reductoisomerase activity GO:0004455	Family Supported Family review supports GO:0004455 FAMILY_WIDE. Every characterized member is an active KARI, both short and long forms. The module uses SF1 as its selector, which is effectively the whole family.
ilvD_activity	biosynthetic dihydroxy-acid dehydratase family NCBIfam:TIGR00110 Family	dihydroxy-acid dehydratase activity GO:0004160	Family Review Missing No supported structured family review is available for NCBIfam:TIGR00110.
leuA_activity	LeuA 2-isopropylmalate synthase family PANTHER:PTHR46911:SF1 Family	2-isopropylmalate synthase activity GO:0003852	Family Supported Family review supports GO:0003852 FAMILY_WIDE. Every characterized primary-metabolism member is an IPMS. The secondary-metabolism SF1 paralogs are named isopropyl malate synthases in UniProt. For htyA the predicted physiological substrate is 4-hydroxyphenylpyruvate rather than 2-oxoisovalerate, which is not enough to declare the IPMS activity absent, so no exception is recorded for the activity. The module selects both SF1 and SF2 for this annoton, which is correct, because S. pombe leu3 and S. cerevisiae LEU4/LEU9 are in different subfamilies.
leuA_activity	LeuA 2-isopropylmalate synthase family PANTHER:PTHR46911:SF2 Family	2-isopropylmalate synthase activity GO:0003852	Family Supported Family review supports GO:0003852 FAMILY_WIDE. Every characterized primary-metabolism member is an IPMS. The secondary-metabolism SF1 paralogs are named isopropyl malate synthases in UniProt. For htyA the predicted physiological substrate is 4-hydroxyphenylpyruvate rather than 2-oxoisovalerate, which is not enough to declare the IPMS activity absent, so no exception is recorded for the activity. The module selects both SF1 and SF2 for this annoton, which is correct, because S. pombe leu3 and S. cerevisiae LEU4/LEU9 are in different subfamilies.
oac1_ipm_transport_activity	fungal mitochondrial oxaloacetate carrier (Oac1) family Family	isopropylmalate transmembrane transporter activity GO:0034658	Family Id Missing The family has no identifier linking it to a curated family review.
leuC_activity	3-isopropylmalate dehydratase large subunit family PANTHER:PTHR43822:SF9 Family	3-isopropylmalate dehydratase activity GO:0003861	Family Supported Family review supports GO:0003861 for PANTHER:PTHR43822:SF9. Safe for SF9 (bacterial LeuC, contributing as the catalytic large subunit of the heteromer; fungal LEU1/leu2, enabling it as monomers) and SF22 (archaeal IPMI/citramalate isomerase). SF2 is listed only because its plant member IIL1 is a genuine IPMI large subunit. The homoaconitases in SF2 (fungal LYS4, methanogen HacA) are excepted. SF21 (Thermus HacA) and SF16 are not included: SF16 has no characterized member in the evidence reviewed here.
leuD_activity	3-isopropylmalate dehydratase small subunit family PANTHER:PTHR43345:SF5 Family	3-isopropylmalate dehydratase activity GO:0003861	Family Supported Family review supports GO:0003861 for PANTHER:PTHR43345:SF5. Safe, as a contribution to the heteromeric enzyme, for bacterial LeuD (SF5), archaeal LeuD (SF9), plant SSU1 (SF2) and the Met-chain-elongation paralogs SSU2/SSU3 (SF7, SF8), which keep IPM-isomerizing capacity. The small subunit carries the substrate-recognition loop, so it shares in the catalysis rather than merely binding the catalytic subunit. Methanogen HacB in SF2 is excepted. SF10 is not listed because its characterized member, Thermus HacB, is a homoaconitase subunit.
leu1_fused_activity	fused fungal isopropylmalate isomerase PANTHER:PTHR43822:SF9 Family	3-isopropylmalate dehydratase activity GO:0003861	Family Supported Family review supports GO:0003861 for PANTHER:PTHR43822:SF9. Safe for SF9 (bacterial LeuC, contributing as the catalytic large subunit of the heteromer; fungal LEU1/leu2, enabling it as monomers) and SF22 (archaeal IPMI/citramalate isomerase). SF2 is listed only because its plant member IIL1 is a genuine IPMI large subunit. The homoaconitases in SF2 (fungal LYS4, methanogen HacA) are excepted. SF21 (Thermus HacA) and SF16 are not included: SF16 has no characterized member in the evidence reviewed here.
leuB_activity	3-isopropylmalate dehydrogenase family PANTHER:PTHR42979:SF1 Family	3-isopropylmalate dehydrogenase activity GO:0003862	Family Supported Family review supports GO:0003862 FAMILY_WIDE. Every assayed member, including glucosinolate-specialized IMDH1, catalyses the reaction with 3-isopropylmalate; IMDH1 merely prefers the methylthio-substituted substrate. Used by the branched-chain amino acid module on SF1 (LeuB/LEU2/leu1) and by the aliphatic glucosinolate module on SF5 (IMDH1).
ilvE_activity	IlvE branched-chain amino-acid aminotransferase family PANTHER:PTHR42825:SF2 Family	branched-chain-amino-acid:2-oxoglutarate transaminase activity GO:0004084	Family Supported Family review supports GO:0004084 FAMILY_WIDE. Shared by proteobacterial IlvE and the Arabidopsis BCATs; BCAT4 retains it as a minor activity. The branched-chain amino acid module lists SF2 (P. putida IlvE) among three PANTHER families that carry this activity, which is consistent with this assessment.
ilvE_activity	IlvE branched-chain amino-acid aminotransferase family PANTHER:PTHR42743:SF11 Family	branched-chain-amino-acid:2-oxoglutarate transaminase activity GO:0004084	Family Supported Family review supports GO:0004084 for PANTHER:PTHR42743:SF11. The IlvE-named members are in SF11 and SF4, but SF11 also holds ADC lyases, which are listed as exceptions. PAINT asserts the activity only for gammaproteobacterial IlvE (PTN000214714). The branched-chain amino acid module lists PTHR42743:SF11 for E. coli IlvE; that is accurate as a classification, but SF11 must not be read as a branched-chain transaminase subfamily, because ABZ2 and SPBC19G7.02 are in it. Arabidopsis At3g05190 (SF11, "BCAT-like protein 1") was not assessed.
ilvE_activity	IlvE branched-chain amino-acid aminotransferase family PANTHER:PTHR11825:SF44 Family	branched-chain-amino-acid:2-oxoglutarate transaminase activity GO:0004084	Family Supported Family review supports GO:0004084 FAMILY_WIDE. The PANTHER subfamily inventory comprises branched-chain aminotransferase, BCAT1 and BCAT2 groups. Rat BCAT2 expression directly produces branched-chain aminotransferase activity with processing of its mitochondrial targeting sequence (PMID:9165094); the human ortholog and reviewed substrate chemistry support the same broad reaction. This supports the reaction across intact members, while the shared class-IV PLP fold alone would not: mitochondrial location, catabolic direction and physiological substrate flux differ among lineages.

Gene-review completeness (33/42 grounded genes reviewed)

31 complete review(s) · 20 with deep research · 9 missing review · 13 reviewed but lacking deep research

Gene	Review	Complete	Deep research
BAT1 P38891	✓	✓	✓
BAT2 P47176	✓	✓	✓
eca39 O14370	✓	✓	✗
ILV1 P00927	✓	✓	✓
ilv1 P36620	✓	✓	✗
ILV2 P07342	✓	✓	✓
ILV3 P39522	✓	✓	✓
ilv3 Q10318	✓	✓	✗
ILV5 P06168	✓	✓	✓
ilv5 P78827	✓	✓	✗
ilv6 O60086	✓	✓	✗
ILV6 P25605	✓	✓	✓
ilvA-I Q88HB4	✓	6/7	✓
ilvA-II Q88CN1	✓	6/7	✗
ilvC Q88DZ0	✓	✓	✓
ilvD Q88CQ2	✓	✓	✗
ilvE Q88H54	✓	✓	✓
ilvH Q88DY9	✓	✓	✓
ilvI Q88DY8	✓	✓	✓
LEU1 P07264	✓	✓	✓
leu1 P18869	✓	✓	✗
leu2 O14289	✓	✓	✗
LEU2 P04173	✓	✓	✓
leu3 O59736	✓	✓	✗
LEU4 P06208	✓	✓	✓
LEU9 Q12166	✓	✓	✓
leuA Q88P28	✓	✓	✗
leuB Q88LE5	✓	✓	✓
leuC Q88LE8	✓	✓	✓
leuD Q88LE7	✓	✓	✓
OAC1 P32332	✓	✓	✓
oac1 Q9UTN1	✓	✓	✗
leuD (Salmonella typhimurium) P04787	✗	—	—
ilvA (Escherichia coli K-12) P04968	✗	—	—
ilvD (Escherichia coli K-12) P05791	✗	—	—
ilvC (Escherichia coli K-12) P05793	✗	—	—
leuC (Escherichia coli K-12) P0A6A6	✗	—	—
ilvE (Escherichia coli K-12) P0AB80	✗	—	—
ilvN (Escherichia coli K-12) P0ADF8	✗	—	—
leuB (Escherichia coli K-12) P30125	✗	—	—
leuA (Corynebacterium glutamicum) P42455	✗	—	—
tda1 O94634	✓	✓	✗

Tree

branched-chain amino acid biosynthesisMetabolic Pathwaybranched_chain_amino_acid_biosynthesis

Parts
1. 1. isoleucine-branch 2-oxobutanoate supply
2. L-threonine to 2-oxobutanoateReactionilvA_step
  
  Annotons
  - Biosynthetic threonine deaminase (IlvA/ILV1) Family: full-length biosynthetic threonine deaminase family
3. 2. acetohydroxy-acid formation
4. Acetohydroxy-acid synthase complexProtein ComplexilvIH_step
  
  Annotons
  - Acetohydroxy-acid synthase catalytic subunit (IlvI/ILV2) Family: biosynthetic acetohydroxy-acid synthase large subunit
  - Acetohydroxy-acid synthase regulatory subunit (IlvH/ILV6) Family: biosynthetic acetohydroxy-acid synthase small subunit
5. 3. acetohydroxy-acid reduction and rearrangement
6. Acetohydroxy acids to dihydroxy acidsReactionilvC_step
  
  Annotons
  - Ketol-acid reductoisomerase (IlvC/ILV5) Family: type I ketol-acid reductoisomerase family
7. 4. branched-chain 2-oxoacid formation
8. Dihydroxy acids to branched-chain 2-oxoacidsReactionilvD_step
  
  Annotons
  - Dihydroxy-acid dehydratase (IlvD/ILV3) Family: biosynthetic dihydroxy-acid dehydratase family
9. 5. leucine-specific carbon-chain extension
10. 2-Oxoisovalerate to 2-oxoisocaproateMetabolic Pathwayleucine_extension
  
  Parts
  1. 1. committed leucine-branch condensation
  2. 2-Oxoisovalerate to 2-isopropylmalateReactionleuA_step
    
    Annotons
    
    2-Isopropylmalate synthase (LeuA/LEU4/LEU9) Family: LeuA 2-isopropylmalate synthase family
  3. 2. 2-isopropylmalate export from mitochondria (fungi) optional
  4. Mitochondrial 2-isopropylmalate exportReactionipm_export_step
    
    Annotons
    
    Mitochondrial carrier exporting 2-isopropylmalate (OAC1) Family: fungal mitochondrial oxaloacetate carrier (Oac1) family
  5. 3. isopropylmalate isomerization
  6. 2-Isopropylmalate to 3-isopropylmalateReactionleuCD_step
    
    Variants
    
    Isopropylmalate isomerase architecture variants by enzyme architecture (Exactly One)
    
    Heteromeric LeuC-LeuD isopropylmalate isomeraseProtein Complexheteromeric_leuCD_variant
    
    Annotons
    
    LeuC 3-isopropylmalate dehydratase large subunit Family: 3-isopropylmalate dehydratase large subunit family
    
    LeuD 3-isopropylmalate dehydratase small subunit Family: 3-isopropylmalate dehydratase small subunit family
    
    Single-chain fused isopropylmalate isomerase (fungal LEU1-type)Reactionsingle_chain_leu1_variant
    
    Annotons
    
    Single-chain isopropylmalate isomerase (LEU1/leu2) Family: fused fungal isopropylmalate isomerase
  7. 4. leucine-branch 2-oxoacid formation
  8. 3-Isopropylmalate to 2-oxoisocaproateReactionleuB_step
    
    Annotons
    
    3-Isopropylmalate dehydrogenase (LeuB/LEU2) Family: 3-isopropylmalate dehydrogenase family
11. 6. terminal transamination of all three branches
12. Branched-chain 2-oxoacids to L-valine, L-leucine, and L-isoleucineReactionilvE_step
  
  Annotons
  - Branched-chain amino-acid aminotransferase (IlvE/BAT1/BAT2) Family: IlvE branched-chain amino-acid aminotransferase family

Details

branched-chain amino acid biosynthesisMetabolic Pathwaybranched_chain_amino_acid_biosynthesis

branched-chain amino acid biosynthetic processGO:0009082 L-valine biosynthetic processGO:0009099 L-isoleucine biosynthetic processGO:1901705 L-leucine biosynthetic processGO:0009098

YeastPathways alignment (BRANCHED-CHAIN-AA-SYN-PWY-1, ILEUSYN-PWY-1, VALSYN-PWY, LEUSYN-PWY-1). All four SGD frames are subsets of this module and no YeastCyc reaction was rejected. Corrections and additions to the YeastCyc gene lists: LEU2 is the 3-isopropylmalate dehydrogenase (RXN-13158 has no gene in the pathway summary); OAC1 exports 2-isopropylmalate from mitochondria (PMID:18682385) and is modelled as an optional fungal transport part; BAT2 is retained as a catalyst but is mainly the catabolic paralog (PMID:21267457). Compartments: the SGD GO-CAM conversions place every activity in the cytosol, but ILV1, ILV2/ILV6, ILV5, ILV3, BAT1, LEU9 and the long LEU4 form are mitochondrial; only LEU1, LEU2, BAT2 and the short LEU4 form are cytosolic (PMID:12626680, PMID:3275644, PMID:8798704). The SGD conversion also types all BAT1/BAT2 reactions as GO:0052656 L-isoleucine transaminase, including the valine and leucine reactions; the module uses the parent GO:0004084. The PomBase model has no valine transamination and no causal edge from tda1 to AHAS, and places one ilv5 activity in GO:0006551 L-leucine metabolic process rather than GO:0009098. S. pombe gene symbols are confusing relative to budding yeast: S. pombe ilv1 is the AHAS catalytic subunit (ILV2 ortholog), tda1 is the threonine deaminase, leu3 is 2-isopropylmalate synthase, leu2 the isomerase and leu1 the dehydrogenase. Upstream supplies (thiamine diphosphate import for AHAS, CoA and acetyl-CoA in mitochondria, Fe-S cluster assembly for ILV3/LEU1), regulators (Leu3/alpha-IPM, Gcn4), tRNA charging and BCAA transport are outside the module. The PSEPK ppu00290 bucket also contains shorter serine/threonine dehydratases, two additional AHAS-like large subunits, AlaA, and leucine dehydrogenase. They are not counted as module members because pathway-map membership alone does not establish that they supply the physiological biosynthetic route. IlvA is required only for the isoleucine precursor input. Its PROVIDES_INPUT_FOR edge records 2-oxobutanoate supply without making IlvA a prerequisite for the pyruvate-only valine branch.

Connections

ilvA_step -> ilvIH_step Provides Input For

ilvIH_step -> ilvC_step Precedes

ilvC_step -> ilvD_step Precedes

ilvD_step -> leucine_extension Precedes

ilvD_step -> ilvE_step Precedes

leucine_extension -> ilvE_step Precedes

Part 1: isoleucine-branch 2-oxobutanoate supply

L-threonine to 2-oxobutanoateReactionilvA_step

Annotons

Biosynthetic threonine deaminase (IlvA/ILV1)

ilvA_activity

Participant: Family: full-length biosynthetic threonine deaminase family

Family:

full-length biosynthetic threonine deaminase familyPANTHER:PTHR48078:SF11

Representative Members: ilvA-I (Pseudomonas putida KT2440)UniProtKB:Q88HB4 ilvA-II (Pseudomonas putida KT2440)UniProtKB:Q88CN1 ilvA (Escherichia coli K-12)UniProtKB:P04968 ILV1 (Saccharomyces cerevisiae)UniProtKB:P00927 tda1 (Schizosaccharomyces pombe)UniProtKB:O94634

Required Function:

threonine deaminase activityGO:0004794

Function

threonine deaminase activityGO:0004794

Substrates: L-threonine

Products: 2-oxobutanoate ammonium

Cofactors: pyridoxal 5'-phosphate

Supplies 2-oxobutanoate for the isoleucine branch; mitochondrial in fungi. KT2440 has two full-length IlvA-family proteins with the same reviewed pathway assignment; their relative physiological contributions remain unresolved.

Part 2: acetohydroxy-acid formation

Acetohydroxy-acid synthase complexProtein ComplexilvIH_step

The catalytic large subunit (bacterial IlvI, fungal ILV2/ilv1) and the non-catalytic regulatory small subunit (bacterial IlvH, fungal ILV6/ilv6) form the complex, which accepts either pyruvate plus pyruvate or pyruvate plus 2-oxobutanoate. In fungi the complex is in the mitochondrial matrix; yeast ILV6 stimulates ILV2 activity up to 7-fold and confers valine feedback sensitivity (PMID:10213630).

acetolactate synthase complexGO:0005948

Annotons

Acetohydroxy-acid synthase catalytic subunit (IlvI/ILV2)

ilvI_activity

Participant: Family: biosynthetic acetohydroxy-acid synthase large subunit

Family:

biosynthetic acetohydroxy-acid synthase large subunitNCBIfam:TIGR00118

Representative Members: ilvI (Pseudomonas putida KT2440)UniProtKB:Q88DY8 ILV2 (Saccharomyces cerevisiae)UniProtKB:P07342 ilv1 (Schizosaccharomyces pombe)UniProtKB:P36620

Required Function:

acetolactate synthase activityGO:0003984

Function

acetolactate synthase activityGO:0003984

Substrates: pyruvate pyruvate or 2-oxobutanoate

Products: 2-acetolactate or 2-aceto-2-hydroxybutanoate carbon dioxide

Cofactors: thiamine diphosphate FAD magnesium ion

Acetohydroxy-acid synthase regulatory subunit (IlvH/ILV6)

ilvH_regulator_activity

Participant: Family: biosynthetic acetohydroxy-acid synthase small subunit

Family:

biosynthetic acetohydroxy-acid synthase small subunit

Representative Members: ilvH (Pseudomonas putida KT2440)UniProtKB:Q88DY9 ilvN (Escherichia coli K-12)UniProtKB:P0ADF8 ILV6 (Saccharomyces cerevisiae)UniProtKB:P25605 ilv6 (Schizosaccharomyces pombe)UniProtKB:O60086

Required Function:

acetolactate synthase regulator activityGO:1990610

Function

acetolactate synthase regulator activityGO:1990610

Regulatory ACT-domain subunit; it contributes activation and valine feedback regulation rather than the acetolactate-forming chemistry. The SGD conversion models it only as a member of the AHAS complex.

Part 3: acetohydroxy-acid reduction and rearrangement

Acetohydroxy acids to dihydroxy acidsReactionilvC_step

Annotons

Ketol-acid reductoisomerase (IlvC/ILV5)

ilvC_activity

Participant: Family: type I ketol-acid reductoisomerase family

Family:

type I ketol-acid reductoisomerase familyPANTHER:PTHR21371:SF1

Representative Members: ilvC (Pseudomonas putida KT2440)UniProtKB:Q88DZ0 ilvC (Escherichia coli K-12)UniProtKB:P05793 ILV5 (Saccharomyces cerevisiae)UniProtKB:P06168 ilv5 (Schizosaccharomyces pombe)UniProtKB:P78827

Required Function:

ketol-acid reductoisomerase activityGO:0004455

Function

ketol-acid reductoisomerase activityGO:0004455

Substrates: 2-acetolactate or 2-aceto-2-hydroxybutanoate NADPH

Products: 2,3-dihydroxy-3-isovalerate or 2,3-dihydroxy-3-methylpentanoate NADP+

Cofactors: magnesium ion

Part 4: branched-chain 2-oxoacid formation

Dihydroxy acids to branched-chain 2-oxoacidsReactionilvD_step

Annotons

Dihydroxy-acid dehydratase (IlvD/ILV3)

ilvD_activity

Participant: Family: biosynthetic dihydroxy-acid dehydratase family

Family:

biosynthetic dihydroxy-acid dehydratase familyNCBIfam:TIGR00110

Representative Members: ilvD (Pseudomonas putida KT2440)UniProtKB:Q88CQ2 ilvD (Escherichia coli K-12)UniProtKB:P05791 ILV3 (Saccharomyces cerevisiae)UniProtKB:P39522 ilv3 (Schizosaccharomyces pombe)UniProtKB:Q10318

Required Function:

dihydroxy-acid dehydratase activityGO:0004160

Function

dihydroxy-acid dehydratase activityGO:0004160

Substrates: 2,3-dihydroxy-3-isovalerate or 2,3-dihydroxy-3-methylpentanoate

Products: 2-oxoisovalerate or 3-methyl-2-oxopentanoate water

Cofactors: iron-sulfur cluster magnesium ion

Part 5: leucine-specific carbon-chain extension

2-Oxoisovalerate to 2-oxoisocaproateMetabolic Pathwayleucine_extension

Three-reaction extension of 2-oxoisovalerate by one carbon. In fungi the first reaction is mostly mitochondrial and the next two are cytosolic, so a mitochondrial carrier exports 2-isopropylmalate; the optional export part is required only where 2-isopropylmalate synthesis and isomerization occur in different compartments.

Connections

leuA_step -> ipm_export_step Precedes

Fungal route with mitochondrial 2-isopropylmalate synthesis.

ipm_export_step -> leuCD_step Precedes

leuA_step -> leuCD_step Precedes

Single-compartment route (prokaryotes; cytosolic LEU4 short form).

leuCD_step -> leuB_step Precedes

Part 1: committed leucine-branch condensation

2-Oxoisovalerate to 2-isopropylmalateReactionleuA_step

Annotons

2-Isopropylmalate synthase (LeuA/LEU4/LEU9)

leuA_activity

Participant: Family: LeuA 2-isopropylmalate synthase family

Family:

LeuA 2-isopropylmalate synthase family

Representative Members: leuA (Pseudomonas putida KT2440)UniProtKB:Q88P28 leuA (Corynebacterium glutamicum)UniProtKB:P42455 LEU4 (Saccharomyces cerevisiae)UniProtKB:P06208 LEU9 (Saccharomyces cerevisiae)UniProtKB:Q12166 leu3 (Schizosaccharomyces pombe)UniProtKB:O59736

Required Function:

2-isopropylmalate synthase activityGO:0003852

Function

2-isopropylmalate synthase activityGO:0003852

Substrates: 2-oxoisovalerate acetyl-CoA water

Products: 2-isopropylmalate coenzyme A

Committed, leucine-feedback-inhibited step of the leucine branch. Mitochondrial in fungi, with a minor cytosolic LEU4 form in budding yeast.

Part 2: 2-isopropylmalate export from mitochondria (fungi) (optional)

Mitochondrial 2-isopropylmalate exportReactionipm_export_step

Annotons

Mitochondrial carrier exporting 2-isopropylmalate (OAC1)

oac1_ipm_transport_activity

Participant: Family: fungal mitochondrial oxaloacetate carrier (Oac1) family

Family:

fungal mitochondrial oxaloacetate carrier (Oac1) family

Representative Members: OAC1 (Saccharomyces cerevisiae)UniProtKB:P32332 oac1 (Schizosaccharomyces pombe)UniProtKB:Q9UTN1

Required Function:

isopropylmalate transmembrane transporter activityGO:0034658

Function

isopropylmalate transmembrane transporter activityGO:0034658

Substrates: 2-isopropylmalate

Products: 2-isopropylmalate

Locations

mitochondrial inner membraneGO:0005743

Moves 2-isopropylmalate from the mitochondrial matrix to the cytosol. Not needed in prokaryotes or where 2-isopropylmalate is made in the cytosol (the short LEU4 form in budding yeast).

Part 3: isopropylmalate isomerization

2-Isopropylmalate to 3-isopropylmalateReactionleuCD_step

Isopropylmalate isomerase dehydrates and rehydrates 2-isopropylmalate to 3-isopropylmalate. The catalytic chemistry is the same in every lineage, but the enzyme is either a heteromeric large-plus-small-subunit complex or a single fused chain.

Variant set: Isopropylmalate isomerase architecture variants by enzyme architecture (Exactly One)

Heteromeric LeuC-LeuD isopropylmalate isomeraseProtein Complexheteromeric_leuCD_variant

3-isopropylmalate dehydratase complexGO:0009316

Bacterial (and plant) architecture with separate large (LeuC) and small (LeuD) subunits.

Annotons

LeuC 3-isopropylmalate dehydratase large subunit

leuC_activity

Participant: Family: 3-isopropylmalate dehydratase large subunit family

Family:

3-isopropylmalate dehydratase large subunit familyPANTHER:PTHR43822:SF9

Representative Members: leuC (Pseudomonas putida KT2440)UniProtKB:Q88LE8 leuC (Escherichia coli K-12)UniProtKB:P0A6A6

Required Function:

3-isopropylmalate dehydratase activityGO:0003861

Function

3-isopropylmalate dehydratase activityGO:0003861

Substrates: 2-isopropylmalate

Products: 3-isopropylmalate

LeuD 3-isopropylmalate dehydratase small subunit

leuD_activity

Participant: Family: 3-isopropylmalate dehydratase small subunit family

Family:

3-isopropylmalate dehydratase small subunit familyPANTHER:PTHR43345:SF5

Representative Members: leuD (Pseudomonas putida KT2440)UniProtKB:Q88LE7 leuD (Salmonella typhimurium)UniProtKB:P04787

Required Function:

3-isopropylmalate dehydratase activityGO:0003861

Function

3-isopropylmalate dehydratase activityGO:0003861

Substrates: 2-isopropylmalate

Products: 3-isopropylmalate

Single-chain fused isopropylmalate isomerase (fungal LEU1-type)Reactionsingle_chain_leu1_variant

Fungal isopropylmalate isomerases (S. cerevisiae LEU1, S. pombe leu2) are single monomeric chains carrying both the large-subunit (TIGR00170) and small-subunit (TIGR00171) regions, whereas bacterial LeuC carries TIGR00170 only (UniProt cross-references). The enzyme is cytosolic (PMID:12626680).

Annotons

Single-chain isopropylmalate isomerase (LEU1/leu2)

leu1_fused_activity

Participant: Family: fused fungal isopropylmalate isomerase

Family:

fused fungal isopropylmalate isomerasePANTHER:PTHR43822:SF9

Representative Members: LEU1 (Saccharomyces cerevisiae)UniProtKB:P07264 leu2 (Schizosaccharomyces pombe)UniProtKB:O14289

Required Function:

3-isopropylmalate dehydratase activityGO:0003861

Function

3-isopropylmalate dehydratase activityGO:0003861

Substrates: 2-isopropylmalate

Products: 3-isopropylmalate

Cofactors: [4Fe-4S] cluster

Locations

cytosolGO:0005829

Part 4: leucine-branch 2-oxoacid formation

3-Isopropylmalate to 2-oxoisocaproateReactionleuB_step

Annotons

3-Isopropylmalate dehydrogenase (LeuB/LEU2)

leuB_activity

Participant: Family: 3-isopropylmalate dehydrogenase family

Family:

3-isopropylmalate dehydrogenase familyPANTHER:PTHR42979:SF1

Representative Members: leuB (Pseudomonas putida KT2440)UniProtKB:Q88LE5 leuB (Escherichia coli K-12)UniProtKB:P30125 LEU2 (Saccharomyces cerevisiae)UniProtKB:P04173 leu1 (Schizosaccharomyces pombe)UniProtKB:P18869

Required Function:

3-isopropylmalate dehydrogenase activityGO:0003862

Function

3-isopropylmalate dehydrogenase activityGO:0003862

Substrates: 3-isopropylmalate NAD+

Products: 2-oxoisocaproate carbon dioxide NADH

Oxidative decarboxylation to 2-oxoisocaproate; cytosolic in fungi.

Part 6: terminal transamination of all three branches

Branched-chain 2-oxoacids to L-valine, L-leucine, and L-isoleucineReactionilvE_step

Annotons

Branched-chain amino-acid aminotransferase (IlvE/BAT1/BAT2)

ilvE_activity

Participant: Family: IlvE branched-chain amino-acid aminotransferase family

Family:

IlvE branched-chain amino-acid aminotransferase family

Representative Members: ilvE (Pseudomonas putida KT2440)UniProtKB:Q88H54 ilvE (Escherichia coli K-12)UniProtKB:P0AB80 BAT1 (Saccharomyces cerevisiae)UniProtKB:P38891 BAT2 (Saccharomyces cerevisiae)UniProtKB:P47176 eca39 (Schizosaccharomyces pombe)UniProtKB:O14370

Required Function:

branched-chain-amino-acid:2-oxoglutarate transaminase activityGO:0004084

Function

branched-chain-amino-acid:2-oxoglutarate transaminase activityGO:0004084

Substrates: 2-oxoisovalerate, 2-oxoisocaproate, or 3-methyl-2-oxopentanoate L-glutamate

Products: L-valine, L-leucine, or L-isoleucine 2-oxoglutarate

Cofactors: pyridoxal 5'-phosphate

A shared reversible enzyme supplies the terminal transamination for the valine, leucine, and isoleucine products. In budding yeast the mitochondrial BAT1 serves mainly biosynthesis and the cytosolic BAT2 mainly catabolism (Ehrlich pathway); either can supply the biosynthetic step, since only the double deletion is auxotrophic. Fission yeast has a single BCAT (eca39).