ACAD8 explained
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
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
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
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.
Further reading
- Näär AM, Beaurang PA, Zhou S, Abraham S, Solomon W, Tjian R . Composite co-activator ARC mediates chromatin-directed transcriptional activation . Nature . 398 . 6730 . 828–32 . Apr 1999 . 10235267 . 10.1038/19789 . 1999Natur.398..828N . 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 . 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 . Nov 2000 . 11013134 . 1288551 . 10.1086/303105 .
- Nguyen TV, Andresen BS, Corydon TJ, Ghisla S, Abd-El Razik N, Mohsen AW, Cederbaum SD, Roe DS, Roe CR, Lench NJ, Vockley J . Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans . Molecular Genetics and Metabolism . 77 . 1–2 . 68–79 . 2003 . 12359132 . 10.1016/S1096-7192(02)00152-X .
- Battaile KP, Nguyen TV, Vockley J, Kim JJ . 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 . Apr 2004 . 14752098 . 10.1074/jbc.M400034200 . free .
- Ma J, Dempsey AA, Stamatiou D, Marshall KW, Liew CC . Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects . Atherosclerosis . 191 . 1 . 63–72 . Mar 2007 . 16806233 . 10.1016/j.atherosclerosis.2006.05.032 .
Notes and References
- Telford EA, Moynihan LM, Markham AF, Lench NJ . 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 . Sep 1999 . 10524212 . 10.1016/s0167-4781(99)00102-5 .
- Web site: Entrez Gene: ACAD8 acyl-Coenzyme A dehydrogenase family, member 8.
- Battaile KP, Nguyen TV, Vockley J, Kim JJ . 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 . 2004 . 14752098 . 10.1074/jbc.M400034200 . free .
- Nguyen TV, Andresen BS, Corydon TJ, Ghisla S, Abd-El Razik N, Mohsen AW, Cederbaum SD, Roe DS, Roe CR, Lench NJ, Vockley J . Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans . Mol. Genet. Metab. . 77 . 1–2 . 68–79 . 2002 . 12359132 . 10.1016/S1096-7192(02)00152-X.
- Isobutyryl-CoA dehydrogenase deficiency. Orphanet. 2007; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=79159. Accessed 2/8/2010.
