Distal L-leucine catabolism

A reusable four-position pathway that converts leucine-derived 3-methylbutanoyl-CoA (isovaleryl-CoA) to acetoacetate and acetyl-CoA. The pathway comprises acyl-CoA dehydrogenation, biotin-dependent carboxylation, methylglutaconyl-CoA hydration, and HMG-CoA cleavage. It separates reaction roles from lineage-specific enzyme families and cellular locations. Upstream leucine transamination and branched-chain 2-oxoacid dehydrogenation are outside the module; the terminal HMG-CoA lyase reaction can also serve other HMG-CoA-generating pathways.

MODULE:leucine_catabolismDRAFTMetabolic Pathwaymodules/leucine_catabolism.yaml
L-leucine catabolic processGO:0006552
GO:0006552
L-leucine catabolic process
GO:0006552 supplies the biological-process context for degradation of L-leucine.
Reactome:R-HSA-70895
Branched-chain amino acid catabolism
Human Reactome provides a curated instance of the ordered distal reactions, while the module abstracts away mitochondrial localization.
file:human/IVD/IVD-ai-review.yaml
Human IVD gene review
P26440 grounds the eukaryotic dehydrogenase instance.
file:human/MCCC1/MCCC1-ai-review.yaml
Human MCCC1 gene review
Q96RQ3 grounds the eukaryotic MCC alpha-subunit role.
file:human/MCCC2/MCCC2-ai-review.yaml
Human MCCC2 gene review
Q9HCC0 grounds the eukaryotic MCC beta-subunit role.
file:human/AUH/AUH-ai-review.yaml
Human AUH gene review
Q13825 grounds the eukaryotic hydratase-family instance.
file:human/HMGCL/HMGCL-ai-review.yaml
Human HMGCL gene review
P35914 grounds the eukaryotic terminal lyase instance.
file:PSEPK/ivd/ivd-ai-review.yaml
PSEPK ivd gene review
Q88FM5 supplies 3-methylbutanoyl-CoA dehydrogenase activity.
file:PSEPK/mccA/mccA-ai-review.yaml
PSEPK mccA gene review
Q88FM2 supplies the MCC biotin-carboxylase/carrier subunit.
file:PSEPK/mccB/mccB-ai-review.yaml
PSEPK mccB gene review
Q88FM4 supplies the MCC carboxyltransferase subunit.
file:PSEPK/liuC/liuC-ai-review.yaml
PSEPK liuC gene review
Q88FM3 supplies the bacterial methylglutaconyl-CoA hydratase.
file:PSEPK/mvaB/mvaB-ai-review.yaml
PSEPK mvaB gene review
Q88H25 supplies a PSEPK HMG-CoA lyase instance.
7Nodes
4Parts
1Variant Sets
2Variants
6Annotons
3Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:leucine_catabolism 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 (10/10 grounded genes reviewed)

10 complete review(s) · 2 with deep research · 0 missing review · 8 reviewed but lacking deep research

Gene Review Complete Deep research
AUH Q13825 ✓ ✓ ✗
HMGCL P35914 ✓ ✓ ✗
IVD P26440 ✓ ✓ ✗
ivd Q88FM5 ✓ ✓ ✗
liuC Q88FM3 ✓ ✓ ✓
mccA Q88FM2 ✓ ✓ ✗
mccB Q88FM4 ✓ ✓ ✗
MCCC1 Q96RQ3 ✓ ✓ ✗
MCCC2 Q9HCC0 ✓ ✓ ✗
mvaB Q88H25 ✓ ✓ ✓

Details

Distal L-leucine catabolismMetabolic Pathwayleucine_catabolism
L-leucine catabolic processGO:0006552

Exact human and bacterial UniProt accessions are exemplars rather than taxonomic restrictions. Mitochondrial matrix localization is valid for eukaryotic instances but is not a pathway-wide requirement and is absent from the reusable module context. Enzyme-bound FAD is represented as the Ivd cofactor rather than a consumed substrate. The distinct eukaryotic AUH and bacterial LiuC hydratase implementations are modeled as alternatives. The bacterial LiuC selector combines a broad crotonase-family record with the exact GO function and a concrete exemplar because the available PANTHER family is not specific for this reaction. No ancestral PTN node is asserted without verified PAINT IBD evidence.

Connections

ivd_step -> mcc_step Provides Input For
Ivd supplies 3-methylcrotonyl-CoA to the MCC complex.
mcc_step -> hydratase_step Provides Input For
MCC supplies 3-methylglutaconyl-CoA to a hydratase.
hydratase_step -> hmgcl_step Provides Input For
Hydration supplies HMG-CoA to the terminal lyase.
Part 1: 3-methylcrotonyl-CoA formation
3-methylbutanoyl-CoA dehydrogenaseReactionivd_step

Annotons

3-methylbutanoyl-CoA dehydrogenase
ivd_activity
Participant: Family: isovaleryl-CoA dehydrogenases
Family:
isovaleryl-CoA dehydrogenasesPANTHER:PTHR43884:SF12
Representative Members: human IVDUniProtKB:P26440 PSEPK IvdUniProtKB:Q88FM5
Required Function:
3-methylbutanoyl-CoA dehydrogenase activityGO:0008470

Function

3-methylbutanoyl-CoA dehydrogenase activityGO:0008470
Substrates: 3-methylbutanoyl-CoA oxidized electron-transfer flavoprotein
Products: 3-methylcrotonyl-CoA reduced electron-transfer flavoprotein

Uses enzyme-bound FAD to transfer reducing equivalents from 3-methylbutanoyl-CoA to an electron-transfer flavoprotein.

Part 2: 3-methylglutaconyl-CoA formation
3-methylcrotonyl-CoA carboxylase complexProtein Complexmcc_step
methylcrotonoyl-CoA carboxylase complexGO:1905202

Annotons

MCC biotin-carboxylase and carrier subunit
mcc_alpha_activity
Participant: Family: MCC alpha subunits
Family:
MCC alpha subunitsPANTHER:PTHR18866:SF33
Representative Members: human MCCC1UniProtKB:Q96RQ3 PSEPK MccAUniProtKB:Q88FM2
Required Function:
biotin carboxylase activityGO:0004075

Function

biotin carboxylase activityGO:0004075
Substrates: biotinylated carrier domain hydrogencarbonate ATP
Products: carboxybiotinylated carrier domain ADP phosphate

Carboxylates its tethered biotin carrier for transfer of the carboxyl group by the beta subunit.

MCC carboxyltransferase subunit
mcc_beta_activity
Participant: Family: MCC beta subunits
Family:
MCC beta subunitsPANTHER:PTHR22855:SF13
Representative Members: human MCCC2UniProtKB:Q9HCC0 PSEPK MccBUniProtKB:Q88FM4
Required Function:
methylcrotonoyl-CoA carboxylase activityGO:0004485

Function

methylcrotonoyl-CoA carboxylase activityGO:0004485
Substrates: 3-methylcrotonyl-CoA carboxybiotinylated carrier domain
Products: 3-methylglutaconyl-CoA biotinylated carrier domain

Transfers the carboxyl group from carrier-bound carboxybiotin to 3-methylcrotonyl-CoA.

Part 3: HMG-CoA formation
Methylglutaconyl-CoA hydrationReactionhydratase_step
Variant set: Methylglutaconyl-CoA hydratase family by enzyme family (One Or More)
AUH-family hydrataseReactioneukaryotic_auh_route

Annotons

AUH methylglutaconyl-CoA hydratase
auh_activity
Participant: Family: AUH-family hydratases
Family:
AUH-family hydratasesPANTHER:PTHR11941:SF12
Representative Members: human AUHUniProtKB:Q13825
Required Function:
methylglutaconyl-CoA hydratase activityGO:0004490

Function

methylglutaconyl-CoA hydratase activityGO:0004490
Substrates: 3-methylglutaconyl-CoA water
Products: (S)-3-hydroxy-3-methylglutaryl-CoA

Hydrates 3-methylglutaconyl-CoA in the eukaryotic AUH family context.

LiuC-family hydrataseReactionbacterial_liuC_route

Annotons

LiuC methylglutaconyl-CoA hydratase
liuC_activity
Participant: Family: function-gated bacterial LiuC crotonase family
Family:
function-gated bacterial LiuC crotonase familyInterPro:IPR001753
Representative Members: PSEPK LiuCUniProtKB:Q88FM3
Required Function:
methylglutaconyl-CoA hydratase activityGO:0004490

Function

methylglutaconyl-CoA hydratase activityGO:0004490
Substrates: 3-methylglutaconyl-CoA water
Products: (S)-3-hydroxy-3-methylglutaryl-CoA

Hydrates 3-methylglutaconyl-CoA in the bacterial LiuC family context.

Part 4: acetoacetate and acetyl-CoA formation
HMG-CoA lyaseReactionhmgcl_step

Annotons

HMG-CoA lyase
hmgcl_activity
Participant: Family: HMG-CoA lyases
Family:
HMG-CoA lyasesPANTHER:PTHR42738
Representative Members: human HMGCLUniProtKB:P35914 PSEPK MvaBUniProtKB:Q88H25
Required Function:
hydroxymethylglutaryl-CoA lyase activityGO:0004419

Function

hydroxymethylglutaryl-CoA lyase activityGO:0004419
Substrates: (S)-3-hydroxy-3-methylglutaryl-CoA
Products: acetoacetate acetyl-CoA

Cleaves HMG-CoA to acetoacetate and acetyl-CoA; this reaction can be shared with other HMG-CoA degradation routes.