|acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain|
|Locus||Chr. 1 p31|
ACADM (acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain) is a gene that provides instructions for making an enzyme called acyl-coenzyme A dehydrogenase that is important for breaking down (degrading) a certain group of fats called medium-chain fatty acids. These fatty acids are found in foods such as milk and certain oils, and they are also stored in the body's fat tissue. Medium-chain fatty acids are also produced when larger fatty acids are degraded. The acyl-coenzyme A dehydrogenase for medium-chain fatty acids (ACADM) enzyme is essential for converting these particular fatty acids to energy, especially during periods without food (fasting). The ACADM enzyme functions in mitochondria, the energy-producing centers within cells. It is found in the mitochondria of several types of tissues, particularly the liver.
Medium-chain acyl-coenzyme A dehydrogenase deficiency can be caused by mutations in the ACADM gene. More than 30 ACADM gene mutations that cause medium-chain acyl-coenzyme A dehydrogenase deficiency have been identified. Many of these mutations switch an amino acid building block in the ACADM enzyme. The most common amino acid substitution replaces lysine with glutamic acid at position 304 in the enzyme's chain of amino acids (also written as Lys304Glu or K304E). This mutation and other amino acid substitutions alter the enzyme's structure, reducing or abolishing its activity. Other mutations delete or duplicate part of the ACADM gene, which leads to an unstable enzyme that cannot function.
With a shortage (deficiency) of functional ACADM enzyme, medium-chain fatty acids cannot be degraded and processed. As a result, these fats are not converted into energy, which can lead to characteristic symptoms of this disorder, such as lack of energy (lethargy) and low blood sugar. Levels of medium-chain fatty acids or partially degraded fatty acids may build up in tissues and can damage the liver and brain, causing more serious complications.
- Gregersen N, Andresen BS, Corydon MJ, Corydon TJ, Olsen RK, Bolund L, Bross P (2001). "Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype-phenotype relationship". Hum Mutat 18 (3): 169–89. doi:10.1002/humu.1174. PMID 11524729.
- Wang SS, Fernhoff PM, Hannon WH, Khoury MJ (1999). "Medium chain acyl-CoA dehydrogenase deficiency human genome epidemiology review". Genet Med 1 (7): 332–9. doi:10.1097/00125817-199911000-00004. PMID 11263545.
- GeneReviews/NIH/NCBI/UW entry on Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency
- ACADM at The GDB Human Genome Database