Mitochondrial fatty acid oxidation disorders (Homo sapiens)

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1, 33DCIEHHADHTrans-D2-enoyl-CoAcis-D3-Enoyl-CoAACADL2,4 Dienoyl-CoA3-Ketoacyl-CoAHADHAHADHSCACADSAcyl-CoA (n-2)SCP2ACADMPECR3-L-Hydroxyacyl-CoAAcetyl-CoALong-chainFA transportersC4-C12Short and medium chain FAs(saturated)Alpha subunitCarnitine palmitoyl-transferase IdeficiencyPlasma membraneCoASHACSL4Long chain acyl-CoACarnitineCPT1AACSL1ACADSLCHAD2Long chain acyl-CoACPT2FAD+ACSL2ACSL3Acyl-CoASLC25A20Long chain acyl-carnitineACADLLong chain acyl-carnitineACADMACADVLSLC22A5Long chain fatty acidC12 FAC14 FACarnitine transporterCarnitineLong chain fatty acidOuter mitochondrial membraneInner mitochondrial membraneCarnitine transporterdeficiencyCarnitine acylcarnitinetranslocasedeficiencyC16 FAC18 FAC15 FAC17 FAC7 FAC8 FAC9 FAC10 FAC4 FAC6 FAC14-C18long chain FAs(saturated)C12 FAC7 FAC8 FAC9 FAC10 FAC4 FAC6 FACarnitineCarnitineCoASHCarnitine palmitoyl- transferase II deficiencyC18 Acyl-CoAC16 Acyl-CoAC14 Acyl-CoAC18 Enoyl-CoAC16 Enoyl-CoAC14 Enoyl-CoAVery long-chainacyl CoAdehydrogenasedeficiencyFADH2Beta-oxidation long-chain substratesMitochondrial trifunctional protein complex (mTFP or MTP)Beta-oxidation short- and medium-chain substratesLCEHBeta subunit2LKAT3-OH acyl-CoA3-ketoacyl-CoAAcetyl-CoAEnoyl-CoAAcetyl-CoAC12 acyl-CoAC16 Acyl-CoAC14 Acyl-CoAH2ONAD+NADH + H+Mitochondrialtrifunctionalprotein deficiencyIsolated deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenaseIsolated deficiency of long-chain 3-ketoacylCoA thiolase


Description

Fatty Acids (FAs) consists of several chain lengths (short, medium and long chain), which all need to be converted to CoA-bound esters to cross the inner mitochondrial membrane. The long-chain lengths however also need additional carnitine esterification.

Several diseases are linked to the proteins in this pathway, which can be categorized into four groups: 1. entry of long-chain FAs into mitochondria disorders; 2. intra-mitochondrial beta-oxidation membrane-bound proteins defects involving long-chain FAs; 3. intra-mitochondrial beta-oxidation matrix proteins defects involving short and medium-chain FAs; 4. impaired electron transfer to Oxidative phosphorylation (OXPHOS) system.

This pathway has been inspired by Chapter 17 of the book of Blau (ISBN 3642403360 (978-3642403361)), edition 4 and build on top of the original 'Mitochondrial long chain fatty acid beta-oxidation pathway'.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Quality Tags

Ontology Terms

 

Bibliography

  1. Blau, N., Duran, M., Gibson, K.M., Donisi-Vici, C.; ''Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, Chapter 17''; ISBN 978-3-642-40337-8, 2014 PubMed Europe PMC Scholia
  2. Xia C, Fu Z, Battaile KP, Kim JP; ''Crystal structure of human mitochondrial trifunctional protein, a fatty acid β-oxidation metabolon.''; Proc Natl Acad Sci U S A, 2019 PubMed Europe PMC Scholia
  3. Rinaldo P, Matern D, Bennett MJ; ''Fatty acid oxidation disorders.''; Annu Rev Physiol, 2002 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
128205view02:13, 29 January 2024EweitzUse standard rectangle for metabolites, standardize case
128204view02:10, 29 January 2024EweitzUse rounded rectangle disease node shapes, mitigate overlap, standardize case
126872view19:40, 28 June 2023KhanspersMinor update
126633view20:22, 7 June 2023KhanspersModified description
126460view19:08, 1 May 2023AlexanderPicofixed citations
126200view13:59, 14 April 2023Ash iyerUpdated omim identifier.
126126view09:16, 11 April 2023Ash iyerModified description
126112view14:00, 7 April 2023EgonwReplaced a CAS number of an enzyme with a ChEBI identifier of the compound
119439view09:35, 29 June 2021DeSlAdded some more diseases; details on mTFP
119421view13:52, 28 June 2021DeSlAdded another disease and FA details
119420view13:38, 28 June 2021DeSlAdded another disease + location of CPT2
119419view13:30, 28 June 2021DeSlAdded short chain FA translocation to inner mitochondrial membrane
119418view13:20, 28 June 2021DeSlAdded more specific IDs for long chain FAs
119417view13:11, 28 June 2021DeSlAdded another ref and disease
119408view12:22, 27 June 2021DeSlAdded general publication
119407view12:20, 27 June 2021DeSlAdded carnitine transport protein + related disease
119406view12:15, 27 June 2021DeSlOntology Term : 'carnitine-acylcarnitine translocase deficiency' added !
119405view12:15, 27 June 2021DeSlOntology Term : 'carnitine-acylcarnitine translocase deficiency' added !
119404view12:15, 27 June 2021DeSlOntology Term : 'carnitine palmitoyltransferase II deficiency' added !
119403view12:15, 27 June 2021DeSlOntology Term : 'carnitine palmitoyltransferase I deficiency pathway' added !
119402view12:14, 27 June 2021DeSlOntology Term : 'carnitine palmitoyltransferase I deficiency' added !
119401view12:13, 27 June 2021DeSlNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
2,4 Dienoyl-CoAMetaboliteType your comment here
3-Ketoacyl-CoAMetaboliteCHEBI:57347 (ChEBI)
3-L-Hydroxyacyl-CoAMetabolite
ACADLGeneProduct33 (Entrez Gene)
ACADLProteinP28330 (Uniprot-TrEMBL) long-chain specific acyl-CoA dehydrogenase
ACADMGeneProduct34 (Entrez Gene)
ACADMProteinP11310 (Uniprot-TrEMBL) medium-chain specific acyl-CoA dehydrogenase
ACADSGeneProduct35 (Entrez Gene)
ACADSProteinP16219 (Uniprot-TrEMBL) short-chain specific acyl-CoA dehydrogenase
ACADVLProteinP49748 (Uniprot-TrEMBL) aka VLCAD
ACSL1GeneProduct2180 (Entrez Gene)
ACSL2GeneProduct80221 (Entrez Gene)
ACSL3GeneProduct2181 (Entrez Gene)
ACSL4GeneProduct2182 (Entrez Gene)
Acetyl-CoAMetabolite72-89-9 (CAS)
Acyl-CoAMetabolite
Acyl-CoA (n-2)MetaboliteCHEBI:17984 (ChEBI)
C10 FAMetaboliteCHEBI:78118 (ChEBI) Annotated with anion ID
C12 FAMetaboliteCHEBI:141075 (ChEBI)
C12 acyl-CoAMetabolite
C14 Acyl-CoAMetabolite
C14 Enoyl-CoAMetabolite
C14 FAMetaboliteCHEBI:140940 (ChEBI)
C15 FAMetaboliteCHEBI:140942 (ChEBI)
C16 Acyl-CoAMetabolite
C16 Enoyl-CoAMetabolite
C16 FAMetaboliteCHEBI:140943 (ChEBI)
C17 FAMetaboliteCHEBI:140945 (ChEBI)
C18 Acyl-CoAMetabolite
C18 Enoyl-CoAMetabolite
C18 FAMetaboliteCHEBI:140947 (ChEBI)
C4 FAMetaboliteCHEBI:78115 (ChEBI) Annotated with anion ID
C6 FAMetaboliteCHEBI:78116 (ChEBI) Annotated with anion ID
C7 FAMetaboliteCHEBI:141070 (ChEBI)
C8 FAMetaboliteCHEBI:141071 (ChEBI)
C9 FAMetaboliteCHEBI:141072 (ChEBI)
CPT1AProtein1374 (Entrez Gene)
CPT2Protein1376 (Entrez Gene)
CarnitineMetaboliteCHEBI:3424 (ChEBI)
CoASHMetaboliteCHEBI:15346 (ChEBI)
DCIGeneProduct1632 (Entrez Gene)
EHHADHGeneProduct1962 (Entrez Gene)
FAD+Metabolite
FADH2Metabolite
HADHAGeneProduct3030 (Entrez Gene) similiar to: ECHA RAT
HADHSCGeneProduct3033 (Entrez Gene)
LCEHProteinP40939 (Uniprot-TrEMBL)
  • long-chain enoyl-CoA hydratase
  • Position 151+173 in amino acid sequence [PMID:30850536]
LCHADProteinP40939 (Uniprot-TrEMBL)
  • long-chain 3-hydroxyacyl-CoA dehydrogenase
  • Position 498+510 in amino acid sequence [PMID:30850536]
LKATProteinP55084 (Uniprot-TrEMBL) long-chain 3-ketoacyl-CoA thiolase
Long chain acyl-CoAMetabolite
Long chain acyl-CoAMetaboliteCHEBI:83139 (ChEBI)
Long chain acyl-carnitineMetabolite
Long chain fatty acidMetaboliteCHEBI:15904 (ChEBI)
PECRGeneProduct55825 (Entrez Gene)
SCP2GeneProduct6342 (Entrez Gene)
SLC22A5GeneProductO76082 (Uniprot-TrEMBL) AKA OCTN2
SLC25A20ProteinO43772 (Uniprot-TrEMBL) AKA CACT
Trans-D2-enoyl-CoAMetaboliteCHEBI:10723 (ChEBI)
cis-D3-Enoyl-CoAMetabolite

Annotated Interactions

No annotated interactions

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