ACAD8

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Acyl-CoA dehydrogenase family, member 8
Protein ACAD8 PDB 1rx0.png
PDB rendering based on 1rx0.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols ACAD8 ; ACAD-8; ARC42
External IDs OMIM604773 MGI1914198 HomoloGene8662 GeneCards: ACAD8 Gene
RNA expression pattern
PBB GE ACAD8 221669 s at tn.png
More reference expression data
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:
134.12 – 134.14 Mb
Chr 9:
26.97 – 27 Mb
PubMed search [1] [2]

Isobutyryl-CoA dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ACAD8 gene on chromosome 11.[1][2]


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[edit]

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.[3]

Clinical significance[edit]

Mutations in ACAD8 have been linked to isobutyryl-CoA dehydrogenase deficiency.[4] Most patients with isobutyryl-CoA dehydrogenase deficiency are asymptotic, but children have also been observed to develop dilated cardiomyopathy.[5]

Function[edit]

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.[6] ACAD8 is responsible for the third step in the breakdown of valine and converts isobutyryl-CoA into methylacrylyl-CoA.

References[edit]

  1. ^ Telford EA, Moynihan LM, Markham AF, Lench NJ (Sep 1999). "Isolation and characterisation of a cDNA encoding the precursor for a novel member of the acyl-CoA dehydrogenase gene family". Biochimica Et Biophysica Acta 1446 (3): 371–6. doi:10.1016/s0167-4781(99)00102-5. PMID 10524212. 
  2. ^ "Entrez Gene: ACAD8 acyl-Coenzyme A dehydrogenase family, member 8". 
  3. ^ Battaile KP, Nguyen TV, Vockley J, Kim JJ (2004). "Structures of isobutyryl-CoA dehydrogenase and enzyme-product complex: comparison with isovaleryl- and short-chain acyl-CoA dehydrogenases". J. Biol. Chem. 279 (16): 16526–34. doi:10.1074/jbc.M400034200. PMID 14752098. 
  4. ^ Nguyen TV, Andresen BS, Corydon TJ, Ghisla S, Abd-El Razik N, Mohsen AW et al. (2002). "Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans". Mol. Genet. Metab. 77 (1-2): 68–79. PMID 12359132. 
  5. ^ Isobutyryl-CoA dehydrogenase deficiency. Orphanet. 2007; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=79159. Accessed 2/8/2010.
  6. ^ Nguyen TV, Andresen BS, Corydon TJ, Ghisla S, Abd-El Razik N, Mohsen AW et al. (2002). "Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans". Mol. Genet. Metab. 77 (1-2): 68–79. PMID 12359132. 

Further reading[edit]