Health Dictionary
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ACAD8
Introduction
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
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.[3]
Clinical significance
Clinical significance
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
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.[4] ACAD8 is responsible for the third step in the breakdown of valine and converts isobutyryl-CoA into methylacrylyl-CoA.
References
References
- ↑ 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.
- ↑ “Entrez Gene: ACAD8 acyl-Coenzyme A dehydrogenase family, member 8”.
- ↑ 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.
- ↑ 4.0 4.1 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”. Mol. Genet. Metab. 77 (1–2): 68–79. doi:10.1016/S1096-7192(02)00152-X. PMID 12359132.
- ↑ 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
External links
- Human ACAD8 genome location and ACAD8 gene details page in the UCSC Genome Browser.
Further reading
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. doi:10.1038/19789. PMID 10235267.
- 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.