Ketone body oxidation (ketolysis)

Mitochondrial oxidation of the ketone bodies D-3-hydroxybutyrate and acetoacetate to acetyl-CoA for entry into the TCA cycle, the route by which extrahepatic tissues (heart, brain, skeletal muscle, renal cortex) use ketone bodies as fuel during fasting. The pathway is three obligate steps: D-3-hydroxybutyrate dehydrogenase (BDH1) oxidises 3-hydroxybutyrate to acetoacetate; succinyl-CoA:3-oxoacid CoA-transferase (OXCT1/SCOT) activates acetoacetate to acetoacetyl-CoA; and acetyl-CoA acetyltransferase (ACAT1, mitochondrial thiolase) thiolytically cleaves acetoacetyl-CoA to two acetyl-CoA. The SCOT step is the committed, irreversible activation step and the metabolic switch that distinguishes ketone-consuming tissues from the liver: the liver produces ketone bodies but does not express OXCT1, so it cannot re-oxidise them and instead exports them. This module is built to be evaluated against tissue expression so that the tissues capable of ketone-body oxidation, and the basis of the liver's inability, can be resolved directly.

MODULE:ketone_body_oxidationDRAFTMetabolic Pathwaymodules/ketone_body_oxidation.yaml
ketolysisGO:0046952
GO:0046952
ketone body catabolic process
Module grounded in the GO biological-process term for ketone body catabolism.
GTEx:gtex_v8
GTEx v8 median gene expression
OXCT1 (SCOT) is expressed in heart, brain, muscle, and kidney but is essentially absent from liver, the molecular basis of the liver's inability to oxidise ketones.
4Nodes
3Parts
0Variant Sets
0Variants
3Annotons
2Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

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.

Gene-review completeness (0/3 grounded genes reviewed)

0 complete review(s) · 0 with deep research · 3 missing review · 0 reviewed but lacking deep research

Gene Review Complete Deep research
ACAT1 (mitochondrial acetyl-CoA acetyltransferase) P24752 ✗ — —
OXCT1 (succinyl-CoA:3-oxoacid CoA-transferase, SCOT) P55809 ✗ — —
BDH1 (D-3-hydroxybutyrate dehydrogenase) Q02338 ✗ — —

Details

Ketone body oxidationMetabolic Pathwayketone_body_oxidation
ketolysisGO:0046952

Linear three-step pathway (all required). UniProt accessions and GO MF/location terms verified. The OXCT1/SCOT step is the discriminator between ketone-oxidising tissues and the liver; see resolve_eukaryotic_abduction.py for the per-tissue abduction against GTEx (liver gap at OXCT1 correctly predicts its inability to consume ketone bodies).

Connections

bdh1_step -> oxct1_step Precedes
oxct1_step -> acat1_step Precedes
Part 1: 3-hydroxybutyrate to acetoacetate
D-3-hydroxybutyrate dehydrogenaseReactionbdh1_step

Annotons

BDH1: D-3-hydroxybutyrate dehydrogenase
BDH1_activity
Participant: Gene: BDH1 (D-3-hydroxybutyrate dehydrogenase)
Gene:
BDH1 (D-3-hydroxybutyrate dehydrogenase)UniProtKB:Q02338

Function

3-hydroxybutyrate dehydrogenase activityGO:0003858
Substrates: (R)-3-hydroxybutyrate NAD+
Products: acetoacetate NADH

Locations

mitochondrionGO:0005739
Part 2: acetoacetate activation (committed step; liver-absent SCOT)
Succinyl-CoA:3-oxoacid CoA-transferase (SCOT)Reactionoxct1_step

Annotons

OXCT1: succinyl-CoA:3-oxoacid CoA-transferase (SCOT)
OXCT1_activity
Participant: Gene: OXCT1 (succinyl-CoA:3-oxoacid CoA-transferase, SCOT)
Gene:
OXCT1 (succinyl-CoA:3-oxoacid CoA-transferase, SCOT)UniProtKB:P55809

Function

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

Locations

mitochondrionGO:0005739

Committed, essentially irreversible activation step. Not expressed in liver, which is therefore unable to oxidise the ketone bodies it makes.

Part 3: thiolytic cleavage to acetyl-CoA
Acetoacetyl-CoA thiolase (ACAT1)Reactionacat1_step

Annotons

ACAT1: mitochondrial acetoacetyl-CoA thiolase
ACAT1_activity
Participant: Gene: ACAT1 (mitochondrial acetyl-CoA acetyltransferase)
Gene:
ACAT1 (mitochondrial acetyl-CoA acetyltransferase)UniProtKB:P24752

Function

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

Locations

mitochondrionGO:0005739