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
Gene location (Human) Chr. Chromosome 11 (human)[1] Band 11q25 Start 134,253,495 bp[1] End 134,265,855 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9|9 A4 Start 26,974,135 bp[2] End 26,999,566 bp[2]
RNA expression pattern 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 • oxidation-reduction process • 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: 26.97 – 27 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.

References

1. GRCh38: Ensembl release 89: ENSG00000151498 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031969 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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 (BBA) - Gene Structure and Expression. 1446 (3): 371–6. doi:10.1016/s0167-4781(99)00102-5. PMID 10524212.
6. "Entrez Gene: ACAD8 acyl-Coenzyme A dehydrogenase family, member 8".
7. 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.
8. Nguyen TV, Andresen BS, Corydon TJ, Ghisla S, Abd-El Razik N, Mohsen AW, Cederbaum SD, Roe DS, Roe CR, Lench NJ, Vockley J (2002). "Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans" (PDF). Mol. Genet. Metab. 77 (1–2): 68–79. doi:10.1016/S1096-7192(02)00152-X. PMID 12359132.
9. Isobutyryl-CoA dehydrogenase deficiency. Orphanet. 2007; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=79159. Accessed 2/8/2010.

External links

• Human ACAD8 genome location and ACAD8 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: Q9UKU7 (Isobutyryl-CoA dehydrogenase, mitochondrial) at the PDBe-KB.

Further reading

• Näär AM, Beaurang PA, Zhou S, Abraham S, Solomon W, Tjian R (Apr 1999). "Composite co-activator ARC mediates chromatin-directed transcriptional activation". Nature. 398 (6730): 828–32. Bibcode:1999Natur.398..828N. doi:10.1038/19789. PMID 10235267. S2CID 23646963.
• Andresen BS, Christensen E, Corydon TJ, Bross P, Pilgaard B, Wanders RJ, Ruiter JP, Simonsen H, Winter V, Knudsen I, Schroeder LD, Gregersen N, Skovby F (Nov 2000). "Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism". American Journal of Human Genetics. 67 (5): 1095–103. doi:10.1086/303105. PMC 1288551. PMID 11013134.
• Nguyen TV, Andresen BS, Corydon TJ, Ghisla S, Abd-El Razik N, Mohsen AW, Cederbaum SD, Roe DS, Roe CR, Lench NJ, Vockley J (2003). "Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans". Molecular Genetics and Metabolism. 77 (1–2): 68–79. doi:10.1016/S1096-7192(02)00152-X. PMID 12359132.
• Battaile KP, Nguyen TV, Vockley J, Kim JJ (Apr 2004). "Structures of isobutyryl-CoA dehydrogenase and enzyme-product complex: comparison with isovaleryl- and short-chain acyl-CoA dehydrogenases". The Journal of Biological Chemistry. 279 (16): 16526–34. doi:10.1074/jbc.M400034200. PMID 14752098.
• Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC (Mar 2007). "Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects". Atherosclerosis. 191 (1): 63–72. doi:10.1016/j.atherosclerosis.2006.05.032. PMID 16806233.