Biology:ACAD8
 Generic protein structure example |
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.
References
- ↑ "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. doi:10.1016/s0167-4781(99)00102-5. PMID 10524212.
- ↑ "Entrez Gene: ACAD8 acyl-Coenzyme A dehydrogenase family, member 8". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=27034.
- ↑ "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. doi:10.1074/jbc.M400034200. PMID 14752098.
- ↑ 4.0 4.1 "Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans". Mol. Genet. Metab. 77 (1–2): 68–79. 2002. doi:10.1016/S1096-7192(02)00152-X. PMID 12359132. https://kops.uni-konstanz.de/bitstream/123456789/7938/1/Identification_of_isobutyryl_CoA_dehydrogenase_and_its_deficiency_in_humans.pdf.
- ↑ 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
- "Composite co-activator ARC mediates chromatin-directed transcriptional activation". Nature 398 (6730): 828–32. Apr 1999. doi:10.1038/19789. PMID 10235267. Bibcode: 1999Natur.398..828N.
- "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. doi:10.1086/303105. PMID 11013134.
- "Identification of isobutyryl-CoA dehydrogenase and its deficiency in humans". Molecular Genetics and Metabolism 77 (1–2): 68–79. 2003. doi:10.1016/S1096-7192(02)00152-X. PMID 12359132. http://nbn-resolving.de/urn:nbn:de:bsz:352-opus-51512.
- "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. doi:10.1074/jbc.M400034200. PMID 14752098.
- "Identifying leukocyte gene expression patterns associated with plasma lipid levels in human subjects". Atherosclerosis 191 (1): 63–72. Mar 2007. doi:10.1016/j.atherosclerosis.2006.05.032. PMID 16806233.
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