ACAD8

Isobutyryl-CoA dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ACAD8 gene on chromosome 11.^[5][6]

ACAD8
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1RX0
Identifiers
Aliases	ACAD8, ACAD-8, ARC42, acyl-CoA dehydrogenase family member 8, IBDH
External IDs	OMIM: 604773; MGI: 1914198; HomoloGene: 8662; GeneCards: ACAD8; OMA:ACAD8 - orthologs
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q25 Start 134,253,548 bp[1] End 134,265,855 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 A4 Start 26,885,431 bp[2] End 26,910,862 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of thyroid gland left lobe of thyroid gland cerebellar hemisphere body of pancreas right hemisphere of cerebellum apex of heart skin of leg skin of abdomen right frontal lobe right lobe of liver Top expressed in right kidney Epithelium of choroid plexus proximal tubule neural layer of retina muscle of thigh granulocyte left lobe of liver human kidney morula spermatocyte More reference expression data BioGPS More reference expression data
Gene ontology Molecular function oxidoreductase activity, acting on the CH-CH group of donors oxidoreductase activity acyl-CoA dehydrogenase activity flavin adenine dinucleotide binding Cellular component mitochondrial matrix mitochondrion Biological process valine catabolic process branched-chain amino acid catabolic process regulation of transcription, DNA-templated transcription, DNA-templated lipid metabolism Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 27034 66948 Ensembl ENSG00000151498 ENSMUSG00000031969 UniProt Q9UKU7 Q9D7B6 RefSeq (mRNA) NM_014384 NM_025862 RefSeq (protein) NP_055199 NP_080138 Location (UCSC) Chr 11: 134.25 – 134.27 Mb Chr 9: 26.89 – 26.91 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The protein encoded by ACAD8 is a mitochondrial protein belongs to the acyl-CoA dehydrogenase family of enzymes, which function to catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branched-chain amino acids. ACAD8 functions in catabolism of the branched-chain amino acid valine.

Structure

ACAD8 functions as a homotetramer and has an overall structure is similar to other acyl-CoA dehydrogenases. The functional protein contains an NH2-terminal alpha-helical domain, a medial beta-strand domain and a C-terminal alpha-helical domain.^[7]

Clinical significance

Mutations in ACAD8 have been linked to isobutyryl-CoA dehydrogenase deficiency.^[8] Most patients with isobutyryl-CoA dehydrogenase deficiency are asymptotic, but children have also been observed to develop dilated cardiomyopathy.^[9]

Function

ACAD8 is an isobutyryl-CoA dehydrogenase that functions in the catabolism of branched-chain amino acids including valine, and shows high reactivity toward isobutyryl-CoA.^[8] ACAD8 is responsible for the third step in the breakdown of valine and converts isobutyryl-CoA into methylacrylyl-CoA.