Ketone-body uptake and oxidation

A reusable pathway for use of D-3-hydroxybutyrate as a carbon and energy source. D-3-hydroxybutyrate is oxidized to acetoacetate, acetoacetate is activated to acetoacetyl-CoA, and a thiolase can cleave acetoacetyl-CoA to acetyl-CoA. Organisms differ in the activation reaction: animal ketolysis generally uses a succinyl-CoA-dependent CoA transferase, whereas some bacteria use an ATP-dependent acetoacetate-CoA ligase. Substrate import is an optional upstream role for organisms that consume extracellular ketone bodies. Intracellular D-3-hydroxybutyrate released from storage-polymer metabolism can enter at the oxidation step. Pseudomonas putida KT2440 provides candidate exemplars for import, oxidation, and ATP-dependent activation; their pathway dominance and the terminal thiolase remain to be resolved experimentally.

MODULE:ketone_body_oxidationDRAFTCONCRETEMetabolic Pathwaymodules/ketone_body_oxidation.yaml
ketone body catabolic processGO:0046952
GO:0046952
ketone body catabolic process
GO:0046952 provides the biological-process boundary for ketone-body utilization.
file:PSEPK/bhbP/bhbP-uniprot.txt
UniProtKB entry for PSEPK BhbP
Q88IC5 is assigned as a D-beta-hydroxybutyrate permease.
file:PSEPK/hbdH/hbdH-uniprot.txt
UniProtKB entry for PSEPK HbdH
Q88IC6 is assigned EC 1.1.1.30 and the 3-hydroxybutyrate dehydrogenase family.
file:PSEPK/aacs/aacs-uniprot.txt
UniProtKB entry for PSEPK Aacs
Q88IC8 is assigned EC 6.2.1.16 and the acetoacetyl-CoA synthetase family.
PMID:26311173
The metabolism of (R)-3-hydroxybutyrate is regulated by the enhancer-binding protein PA2005 and the alternative sigma factor RpoN in Pseudomonas aeruginosa PAO1.
A Pseudomonas model establishes D-3-hydroxybutyrate oxidation to acetoacetate while noting that the genus does not generally produce PHB.
PMID:10735852
Requirement for the enzymes acetoacetyl coenzyme A synthetase and poly-3-hydroxybutyrate (PHB) synthase for growth of Sinorhizobium meliloti on PHB cycle intermediates.
Sinorhizobium genetics establish ATP-dependent acetoacetate activation as a bacterial alternative to CoA-transferase activation.
file:projects/P_PUTIDA/data/psepk_pathway_membership.tsv
PSEPK pathway membership table
The local ppu00650 membership includes hbdH and aacs in butanoate metabolism, while the adjacent bhbP permease supplies the pathway input.
file:projects/P_PUTIDA/data/psepk_gene_list.tsv
PSEPK gene inventory
The exact Q88GH0/PP_3754 record assigns BktB both EC 2.3.1.9 and EC 2.3.1.16, establishing reaction capability but not which thiolase is used physiologically in D-3-hydroxybutyrate catabolism.

This revision removes the previous mammal-only tissue framing and models the conserved chemistry with taxon-dependent acetoacetate-activation variants. CONCRETE denotes the defined reaction topology, while family participants keep the pathway reusable across taxa. KT2440 BhbP, HbdH, Aacs, and BktB are candidates grounded to exact UniProt accessions, not experimentally proven assignments. Storage-polymer-derived D-3-hydroxybutyrate is a possible intracellular entry in bacteria, but KT2440 is known primarily for medium-chain-length PHA and its substrate source here remains unresolved.

7Nodes
4Parts
1Variant Sets
2Variants
5Annotons
3Connections

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:ketone_body_oxidation 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.

  • hydroxybutyrate_import → hydroxybutyrate_oxidation [NOT_CHECKED]
  • hydroxybutyrate_oxidation → acetoacetate_activation [NOT_CHECKED]
  • acetoacetate_activation → acetoacetyl_coa_thiolysis [VERIFIED]
    shared: acetoacetylcoa, coa
    Both activation variants produce acetoacetyl-CoA, which the downstream thiolase cleaves to two acetyl-CoA molecules. The automated GO-to-RHEA string check may miss the SCOT branch because that reaction can use the generic class 3-oxoacyl-CoA while the thiolase reaction names the specific member acetoacetyl-CoA; the class relationship is not visible to the string matcher.

Gene-review completeness (6/7 grounded genes reviewed)

5 complete review(s) · 0 with deep research · 1 missing review · 6 reviewed but lacking deep research

Gene Review Complete Deep research
aacs Q88IC8 ✓ ✓ ✗
ACAT1 P24752 ✓ 43/49 ✗
BDH1 Q02338 ✓ ✓ ✗
bhbP Q88IC5 ✓ ✓ ✗
hbdH Q88IC6 ✓ ✓ ✗
OXCT1 P55809 ✓ ✓ ✗
BktB (PSEPK candidate) Q88GH0 ✗ — —

Details

Ketone-body uptake and oxidationMetabolic Pathwayketone_body_oxidation
ketone body catabolic processGO:0046952

Connections

Part 1: optional uptake of extracellular D-3-hydroxybutyrate (optional)
D-3-hydroxybutyrate importTransport Stephydroxybutyrate_import

A membrane permease imports D-3-hydroxybutyrate when the substrate is supplied extracellularly; intracellular ketone-body pathways do not require this part.

Annotons

D-3-hydroxybutyrate permease
bhbp_hydroxybutyrate_permease
Participant: Family: bacterial Gnt-family D-3-hydroxybutyrate permeases
Family:
bacterial Gnt-family D-3-hydroxybutyrate permeasesInterPro:IPR003474
Representative Members: BhbP (PSEPK candidate)UniProtKB:Q88IC5

Function

monocarboxylic acid transmembrane transporter activityGO:0008028
Substrates: extracellular D-3-hydroxybutyrate
Products: intracellular D-3-hydroxybutyrate

Processes

carboxylic acid transmembrane transportGO:1905039

Locations

plasma membraneGO:0005886

Supplies extracellular D-3-hydroxybutyrate to the catabolic reactions.

Part 2: D-3-hydroxybutyrate oxidation to acetoacetate
D-3-hydroxybutyrate oxidationReactionhydroxybutyrate_oxidation

Annotons

D-3-hydroxybutyrate dehydrogenase
hbdh_activity
Participant: Family: 3-hydroxybutyrate dehydrogenase family
Family:
3-hydroxybutyrate dehydrogenase familyInterPro:IPR011294
Representative Members: HbdH (PSEPK candidate)UniProtKB:Q88IC6 BDH1 (human exemplar)UniProtKB:Q02338

Function

3-hydroxybutyrate dehydrogenase activityGO:0003858
Substrates: D-3-hydroxybutyrate NAD+
Products: acetoacetate NADH

Processes

ketone body catabolic processGO:0046952

Oxidizes D-3-hydroxybutyrate to acetoacetate.

Part 3: acetoacetate activation to acetoacetyl-CoA
Acetoacetate activationReactionacetoacetate_activation
Variant set: Acetoacetate activation route by CoA-transfer chemistry (Exactly One)

Ketone-body consumers can activate acetoacetate by CoA transfer from succinyl-CoA or by ATP-dependent ligation of free coenzyme A.

Succinyl-CoA-dependent SCOT activationReactionscot_activation

Annotons

Succinyl-CoA:3-oxoacid CoA-transferase
oxct_scot_activity
Participant: Gene: OXCT1 (human SCOT exemplar)
Gene:
OXCT1 (human SCOT exemplar)UniProtKB:P55809

Function

succinyl-CoA:3-oxo-acid CoA-transferase activityGO:0008260
Substrates: acetoacetate succinyl-CoA
Products: acetoacetyl-CoA succinate

CoA-transferase implementation characteristic of animal ketolysis.

ATP-dependent acetoacetate-CoA ligase activationReactionaacs_activation

Annotons

Acetoacetate-CoA ligase
aacs_ligase_activity
Participant: Family: acetoacetyl-CoA synthetase family
Family:
acetoacetyl-CoA synthetase familyPANTHER:PTHR42921:SF1
Representative Members: Aacs (PSEPK candidate)UniProtKB:Q88IC8

Function

acetoacetate-CoA ligase activityGO:0030729
Substrates: acetoacetate coenzyme A ATP
Products: acetoacetyl-CoA AMP diphosphate

ATP-dependent bacterial acetoacetate-activation route.

Part 4: acetoacetyl-CoA cleavage to acetyl-CoA
Acetoacetyl-CoA thiolysisReactionacetoacetyl_coa_thiolysis

Annotons

Acetyl-CoA C-acetyltransferase
thiolase_activity
Participant: Family: acetyl-CoA acetyltransferase family
Family:
acetyl-CoA acetyltransferase familyInterPro:IPR002155
Representative Members: ACAT1 (human exemplar)UniProtKB:P24752 BktB (PSEPK candidate)UniProtKB:Q88GH0

Function

acetyl-CoA C-acetyltransferase activityGO:0003985
Substrates: acetoacetyl-CoA coenzyme A
Products: 2 acetyl-CoA

Processes

ketone body catabolic processGO:0046952

Cleaves activated acetoacetate to two acetyl-CoA molecules.