L-Carnitine Degradation I
PathBank:SMP0002051
The four-reaction PathBank route represents anaerobic L-carnitine reduction to gamma-butyrobetaine through CoA thioesters, using characterized Escherichia coli K-12 Cai proteins. CaiC supplies the initial carnitinyl-CoA pool; CaiD dehydrates it, CaiA reduces crotonobetainyl-CoA, and the CaiB homodimer transfers CoA to another carnitine molecule, releasing gamma-butyrobetaine and regenerating carnitinyl-CoA. Thus ATP-dependent initiation is distinct from the recycling loop. Rhea charge forms and both generic electron-transfer flavoprotein redox states are retained; the exact physiological donor complex is unresolved. FAD bound to CaiA is a separate cofactor. Selected catabolic directions do not imply irreversibility of CaiD or CaiB. This enzyme mechanism does not establish growth or expression in every K-12 strain, and is distinct from aerobic carnitine assimilation. The older native map defines the route boundary; its erroneous or underspecified chemical xrefs are not adopted as exact identities.
- Pathway type
- anaerobic carnitine catabolism
- Organism scope
Pathway network
24 nodes · 32 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
- Pathway
- Solid arrow: mechanistic relation
- Dashed arrow: membership, location or cofactor relation
Components and activities
| Node | Kind or role | Source direction |
|---|---|---|
Escherichia coli K-12NCBITaxon:83333 | taxon | |
(R)-carnitineCHEBI:16347 | small molecule | |
ATP(4-)CHEBI:30616 | small molecule | |
coenzyme A(4-)CHEBI:57287 | small molecule | |
(R)-carnitinyl-CoA(3-)CHEBI:60932 | small molecule | |
adenosine 5'-monophosphate(2-)CHEBI:456215 | small molecule | |
diphosphate(3-)CHEBI:33019 | small molecule | |
(E)-4-(trimethylammonio)but-2-enoyl-CoA(3-)CHEBI:60933 | small molecule | |
waterCHEBI:15377 | small molecule | |
gamma-butyrobetainyl-CoA(3-)CHEBI:61513 | small molecule | |
hydronCHEBI:15378 | small molecule | |
4-(trimethylammonio)butanoateCHEBI:16244 | small molecule | |
FAD(3-)CHEBI:57692 | cofactor | |
oxidized [electron-transfer flavoprotein]RHEA-COMP:10685 | protein | |
reduced [electron-transfer flavoprotein]RHEA-COMP:10686 | protein | |
Crotonobetaine/carnitine--CoA ligaseUniProtKB:P31552 | protein | |
Carnitinyl-CoA dehydrataseUniProtKB:P31551 | protein | |
Crotonobetainyl-CoA reductaseUniProtKB:P60584 | protein | |
L-carnitine CoA-transferaseUniProtKB:P31572 | protein | |
γ-butyrobetainyl-CoA:carnitine CoA transferasePathBank:SMP0002051/ProteinComplex/4010 | complex | |
CaiC ATP-dependent initial carnitinyl-CoA formationRHEA:28515 | molecular activity | left to right |
CaiD carnitinyl-CoA dehydrationRHEA:28339 | molecular activity | left to right |
CaiA crotonobetainyl-CoA reductionRHEA:51586 | molecular activity | right to left |
CaiB CoA transfer to carnitine and gamma-butyrobetaine releaseRHEA:28419 | molecular activity | left to right |
Mechanistic edges
| Subject | Predicate and description | Object | Evidence |
|---|---|---|---|
(R)-carnitineCHEBI:16347 | consumes | CaiC ATP-dependent initial carnitinyl-CoA formationRHEA:28515 |
|
ATP(4-)CHEBI:30616 | consumes | CaiC ATP-dependent initial carnitinyl-CoA formationRHEA:28515 |
|
coenzyme A(4-)CHEBI:57287 | consumes | CaiC ATP-dependent initial carnitinyl-CoA formationRHEA:28515 |
|
CaiC ATP-dependent initial carnitinyl-CoA formationRHEA:28515 | produces | (R)-carnitinyl-CoA(3-)CHEBI:60932 |
|
CaiC ATP-dependent initial carnitinyl-CoA formationRHEA:28515 | produces | adenosine 5'-monophosphate(2-)CHEBI:456215 |
|
CaiC ATP-dependent initial carnitinyl-CoA formationRHEA:28515 | produces | diphosphate(3-)CHEBI:33019 |
|
(R)-carnitinyl-CoA(3-)CHEBI:60932 | consumes | CaiD carnitinyl-CoA dehydrationRHEA:28339 |
|
CaiD carnitinyl-CoA dehydrationRHEA:28339 | produces | (E)-4-(trimethylammonio)but-2-enoyl-CoA(3-)CHEBI:60933 |
|
CaiD carnitinyl-CoA dehydrationRHEA:28339 | produces | waterCHEBI:15377 |
|
(E)-4-(trimethylammonio)but-2-enoyl-CoA(3-)CHEBI:60933 | consumes | CaiA crotonobetainyl-CoA reductionRHEA:51586 |
|
reduced [electron-transfer flavoprotein]RHEA-COMP:10686 | consumes This is a whole generic electron-transfer flavoprotein redox state, not free FAD/FADH2 and not an identified FixA/FixB complex. Coefficient 1 belongs to the Rhea reference equation. | CaiA crotonobetainyl-CoA reductionRHEA:51586 |
|
CaiA crotonobetainyl-CoA reductionRHEA:51586 | produces | gamma-butyrobetainyl-CoA(3-)CHEBI:61513 |
|
CaiA crotonobetainyl-CoA reductionRHEA:51586 | produces This is a whole generic electron-transfer flavoprotein redox state, not free FAD/FADH2 and not an identified FixA/FixB complex. Coefficient 1 belongs to the Rhea reference equation. | oxidized [electron-transfer flavoprotein]RHEA-COMP:10685 |
|
CaiA crotonobetainyl-CoA reductionRHEA:51586 | produces | hydronCHEBI:15378 |
|
gamma-butyrobetainyl-CoA(3-)CHEBI:61513 | consumes | CaiB CoA transfer to carnitine and gamma-butyrobetaine releaseRHEA:28419 |
|
(R)-carnitineCHEBI:16347 | consumes | CaiB CoA transfer to carnitine and gamma-butyrobetaine releaseRHEA:28419 |
|
CaiB CoA transfer to carnitine and gamma-butyrobetaine releaseRHEA:28419 | produces | (R)-carnitinyl-CoA(3-)CHEBI:60932 |
|
CaiB CoA transfer to carnitine and gamma-butyrobetaine releaseRHEA:28419 | produces | 4-(trimethylammonio)butanoateCHEBI:16244 |
|
Crotonobetaine/carnitine--CoA ligaseUniProtKB:P31552 | catalyzes CaiC primes the CoA-linked cycle; this ATP-dependent step does not imply one ATP hydrolyzed per subsequent carnitine reduction. Its other betaine substrates lie outside this native four-reaction route. | CaiC ATP-dependent initial carnitinyl-CoA formationRHEA:28515 |
|
Carnitinyl-CoA dehydrataseUniProtKB:P31551 | catalyzes The protein accession denotes CaiD enzyme identity; UniProt describes a homotrimer. The catabolic dehydration direction is selected from a reversible hydration/dehydration reaction, not a free-carnitine dehydratase reaction. | CaiD carnitinyl-CoA dehydrationRHEA:28339 |
|
Crotonobetainyl-CoA reductaseUniProtKB:P60584 | catalyzes The protein accession denotes CaiA enzyme identity; UniProt describes a homotetramer. The selected right-to-left direction of Rhea 51584 reduces crotonobetainyl-CoA. Genetic requirement for fixA/fixB does not identify a directly measured physiological carrier complex or its electron-transfer stoichiometry. | CaiA crotonobetainyl-CoA reductionRHEA:51586 |
|
γ-butyrobetainyl-CoA:carnitine CoA transferasePathBank:SMP0002051/ProteinComplex/4010 | catalyzes The native CaiB homodimer transfers CoA from gamma-butyrobetainyl-CoA to fresh carnitine. The selected direction releases gamma-butyrobetaine and regenerates carnitinyl-CoA; the characterized CoA transfer is reversible. | CaiB CoA transfer to carnitine and gamma-butyrobetaine releaseRHEA:28419 |
|
γ-butyrobetainyl-CoA:carnitine CoA transferasePathBank:SMP0002051/ProteinComplex/4010 | has_part Two copies of CaiB form the source-defined homodimer; the graph represents membership once and preserves the copy number here and in the evidence. | L-carnitine CoA-transferaseUniProtKB:P31572 |
|
Crotonobetainyl-CoA reductaseUniProtKB:P60584 | has_cofactor This is FAD bound to CaiA, separate from the flavin reactive part of the generic electron-transfer flavoprotein in the Rhea redox reaction. The ChEBI charge form follows the curated cofactor cross-reference. | FAD(3-)CHEBI:57692 |
|
CaiC ATP-dependent initial carnitinyl-CoA formationRHEA:28515 | part_of Manual source correspondence based on the native catalyst and biochemical transformation, not a native Rhea cross-reference or exactMatch. Current Rhea chemistry supplies explicit charge/stereo forms and corrects the older map's chemical-identity defects. | PathBank:SMP0002051 |
|
CaiD carnitinyl-CoA dehydrationRHEA:28339 | part_of Manual source correspondence based on the native catalyst and biochemical transformation, not a native Rhea cross-reference or exactMatch. Current Rhea chemistry supplies explicit charge/stereo forms and corrects the older map's chemical-identity defects. | PathBank:SMP0002051 |
|
CaiA crotonobetainyl-CoA reductionRHEA:51586 | part_of Manual source correspondence based on the native catalyst and biochemical transformation, not a native Rhea cross-reference or exactMatch. Current Rhea chemistry supplies explicit charge/stereo forms and corrects the older map's chemical-identity defects. | PathBank:SMP0002051 |
|
CaiB CoA transfer to carnitine and gamma-butyrobetaine releaseRHEA:28419 | part_of Manual source correspondence based on the native catalyst and biochemical transformation, not a native Rhea cross-reference or exactMatch. Current Rhea chemistry supplies explicit charge/stereo forms and corrects the older map's chemical-identity defects. | PathBank:SMP0002051 |
|
CaiC ATP-dependent initial carnitinyl-CoA formationRHEA:28515 | provides_input_for CaiC supplies the initial carnitinyl-CoA pool for CaiD; the subsequent CaiB loop recycles that pool. | CaiD carnitinyl-CoA dehydrationRHEA:28339 |
|
CaiD carnitinyl-CoA dehydrationRHEA:28339 | provides_input_for The product CHEBI:60933 is the next selected reaction substrate. | CaiA crotonobetainyl-CoA reductionRHEA:51586 |
|
CaiA crotonobetainyl-CoA reductionRHEA:51586 | provides_input_for The product CHEBI:61513 is the next selected reaction substrate. | CaiB CoA transfer to carnitine and gamma-butyrobetaine releaseRHEA:28419 |
|
CaiB CoA transfer to carnitine and gamma-butyrobetaine releaseRHEA:28419 | provides_input_for CaiB regenerates carnitinyl-CoA for another cycle; this material-flow loop does not assert a temporal order from the native pathwayOrder array. | CaiD carnitinyl-CoA dehydrationRHEA:28339 |
|
References
PathBank:SMP0002051PathBank L-Carnitine Degradation I, native BioPAX member PW002037.owl (source version: primary archive Last-Modified 2019-08-16; member PW002037.owl)RHEA:28515Rhea 28515 directed carnitine pathway reaction (source version: 142 (2026-09-02))RHEA:28339Rhea 28339 directed carnitine pathway reaction (source version: 142 (2026-09-02))RHEA:51586Rhea 51586 directed carnitine pathway reaction (source version: 142 (2026-09-02))RHEA:28419Rhea 28419 directed carnitine pathway reaction (source version: 142 (2026-09-02))UniProtKB:P31552UniProtKB P31552, Escherichia coli K-12 (source version: 2026_03)UniProtKB:P31551UniProtKB P31551, Escherichia coli K-12 (source version: 2026_03)UniProtKB:P60584UniProtKB P60584, Escherichia coli K-12 (source version: 2026_03)UniProtKB:P31572UniProtKB P31572, Escherichia coli K-12 (source version: 2026_03)PMID:18266698Role of betaine:CoA ligase (CaiC) in the activation of betaines and the transfer of coenzyme A in Escherichia coli.PMID:11551212Involvement of coenzyme A esters and two new enzymes, an enoyl-CoA hydratase and a CoA-transferase, in the hydration of crotonobetaine to L-carnitine by Escherichia coli.PMID:15518548Crystal structure of CaiB, a type-III CoA transferase in carnitine metabolism.PMID:10209289Crotonobetaine reductase from Escherichia coli consists of two proteins.PMID:12081978The fixA and fixB genes are necessary for anaerobic carnitine reduction in Escherichia coli.PMID:10978161Isolation, identification, and synthesis of gamma-butyrobetainyl-CoA and crotonobetainyl-CoA, compounds involved in carnitine metabolism of E. coli.PMID:8060125Crotonobetaine reductase from Escherichia coli--a new inducible enzyme of anaerobic metabolization of L(-)-carnitine.PMID:8631699Identification and characterization of the caiF gene encoding a potential transcriptional activator of carnitine metabolism in Escherichia coli.PMID:7815937Molecular characterization of the cai operon necessary for carnitine metabolism in Escherichia coli.
Curation history
- Codex
- CREATE — Curated the anaerobic carnitine CoA pathway and carrier states
Added PathBank SMP0002051 with four Rhea-directed reactions, whole oxidized and reduced electron-transfer flavoprotein states, a CaiB homodimer and CaiA-bound FAD. Native chemical cross-reference defects and the distinction between initial CoA activation and recycling are documented in research/pathway_additions/2026-10-10-carnitine-putrescine. No exact physiological donor complex or universal K-12 growth claim is inferred.
- CREATE — Curated the anaerobic carnitine CoA pathway and carrier states