Mitochondrial fatty acid oxidation disorders (Homo sapiens)

From WikiPathways

Revision as of 19:40, 28 June 2023 by Khanspers (Talk | contribs)
Jump to: navigation, search
2, 32cis-D3-Enoyl-CoADCIAcyl-CoA (n-2)3-Ketoacyl-CoAACADSACADMSCP2EHHADHACADLAcetyl-CoAHADHAPECRHADHSC2,4 Dienoyl-CoAtrans-D2-Enoyl-CoA3-L-Hydroxyacyl-CoALong-chainFA transportersC4-C12Short+medium chain FAs(saturated)alpha subunitCarnitine palmitoyl-transferase IdeficiencyPlasma MembraneCoASHACSL4Long chain Acyl-CoACarnitineCPT1AACSL1ACADSLCHAD1Long 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+medium-chain substratesLCEHbeta subunit1LKAT3-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

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

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
134493view05:27, 22 July 2024EgonwRemoved a template comment
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 Fatty AcidMetaboliteCHEBI:15904 (ChEBI)
Long chain Acyl-CoAMetabolite
Long chain Acyl-CoAMetaboliteCHEBI:83139 (ChEBI)
Long chain acyl-carnitineMetabolite
PECRGeneProduct55825 (Entrez Gene)
SCP2GeneProduct6342 (Entrez Gene)
SLC22A5GeneProductO76082 (Uniprot-TrEMBL) AKA OCTN2
SLC25A20ProteinO43772 (Uniprot-TrEMBL) AKA CACT
cis-D3-Enoyl-CoAMetabolite
trans-D2-Enoyl-CoAMetaboliteCHEBI:10723 (ChEBI)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5123"
Personal tools