Mitochondrial fatty acid oxidation disorders (WP5123)

Homo sapiens

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 [https://www.wikipathways.org/instance/WP368_r117795 'Mitochondrial long chain fatty acid beta-oxidation pathway']. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP368 CPTAC Assay Portal]

Authors

Denise Slenter , Egon Willighagen , Aishwarya Iyer , Alex Pico , Kristina Hanspers , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Inherited Metabolic Disorders (IMD) Pathways

Annotations

Pathway Ontology

fatty acid beta degradation pathway carnitine palmitoyltransferase I deficiency pathway fatty acid beta degradation pathway carnitine-acylcarnitine translocase deficiency classic metabolic pathway

Disease Ontology

carnitine palmitoyltransferase II deficiency carnitine palmitoyltransferase I deficiency carnitine-acylcarnitine translocase deficiency

Participants

Label Type Compact URI Comment
3-Ketoacyl-CoA Metabolite chebi:57347
Acetyl-CoA Metabolite cas:72-89-9
Trans-D2-enoyl-CoA Metabolite chebi:10723
Acyl-CoA (n-2) Metabolite chebi:17984
CoASH Metabolite chebi:15346
Long chain acyl-CoA Metabolite chebi:83139
Carnitine Metabolite chebi:3424
Long chain fatty acid Metabolite chebi:15904
C12 FA Metabolite chebi:141075
C14 FA Metabolite chebi:140940
C16 FA Metabolite chebi:140943
C18 FA Metabolite chebi:140947
C15 FA Metabolite chebi:140942
C17 FA Metabolite chebi:140945
C7 FA Metabolite chebi:141070
C8 FA Metabolite chebi:141071
C9 FA Metabolite chebi:141072
C10 FA Metabolite chebi:78118 Annotated with anion ID
C4 FA Metabolite chebi:78115 Annotated with anion ID
C6 FA Metabolite chebi:78116 Annotated with anion ID
SCP2 GeneProduct ncbigene:6342
EHHADH GeneProduct ncbigene:1962
DCI GeneProduct ncbigene:1632
ACADS GeneProduct ncbigene:35
HADHA GeneProduct ncbigene:3030 similiar to: ECHA RAT
ACADL GeneProduct ncbigene:33
ACADM GeneProduct ncbigene:34
HADHSC GeneProduct ncbigene:3033
PECR GeneProduct ncbigene:55825
ACSL4 GeneProduct ncbigene:2182
ACSL1 GeneProduct ncbigene:2180
ACSL2 GeneProduct ncbigene:80221
ACSL3 GeneProduct ncbigene:2181
SLC22A5 GeneProduct uniprot:O76082 AKA OCTN2
CPT1A Protein ncbigene:1374
ACADS Protein uniprot:P16219 short-chain specific acyl-CoA dehydrogenase
LCHAD Protein uniprot:P40939 long-chain 3-hydroxyacyl-CoA dehydrogenase
Position 498+510 in amino acid sequence [PMID:30850536]
CPT2 Protein ncbigene:1376
SLC25A20 Protein uniprot:O43772 AKA CACT
ACADL Protein uniprot:P28330 long-chain specific acyl-CoA dehydrogenase
ACADM Protein uniprot:P11310 medium-chain specific acyl-CoA dehydrogenase
ACADVL Protein uniprot:P49748 aka VLCAD
LCEH Protein uniprot:P40939 long-chain enoyl-CoA hydratase
Position 151+173 in amino acid sequence [PMID:30850536]
LKAT Protein uniprot:P55084 long-chain 3-ketoacyl-CoA thiolase

References

  1. Fatty acid oxidation disorders. Rinaldo P, Matern D, Bennett MJ. Annu Rev Physiol. 2002;64:477–502. PubMed Europe PMC Scholia
  2. Crystal structure of human mitochondrial trifunctional protein, a fatty acid β-oxidation metabolon. Xia C, Fu Z, Battaile KP, Kim JJP. Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6069–74. PubMed Europe PMC Scholia