ACADM
| ACADM | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | ACADM,acyl-CoA dehydrogenase, C-4 to C-12 straight chain, ACAD1, MCAD, MCADH, acyl-CoA dehydrogenase medium chain | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM:607008;MGI:87867;HomoloGene:3;GeneCards:ACADM;OMA:ACADM - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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ACADM(acyl-Coenzyme A dehydrogenase, C-4 to C-12 straight chain) is agenethat provides instructions for making an enzyme calledacyl-coenzyme A dehydrogenasethat is important for breaking down (degrading) a certain group of fats calledmedium-chain fatty acids.
Thesefatty acidsare found in foods such asmilkand certainoils,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 themitochondriaof several types of tissues, particularly theliver.
The ACADM gene is located on the short (p) arm ofchromosome 1at position 31, frombase pair75,902,302 to base pair 75,941,203.
Structure[edit]
The protein encoded by theACADMgene is ~47 kDa in size, and composed of 421 amino acids.[5]
Function[edit]
The LCAD enzyme catalyzes most of fatty acid beta-oxidation by forming a C2-C3 trans-double bond in the fatty acid. MCAD works on long-chain fatty acids, typically between C4 and C12-acylCoA.[6]Fatty acid oxidation has proven to spare glucose in fasting conditions, and is also required for amino acid metabolism, which is essential for the maintenance of adequate glucose production.[7]Furthermore, MCAD participates in fatty acid metabolism and PPAR signaling pathway.[8]
Clinical significance[edit]
Medium-chain acyl-coenzyme A dehydrogenase deficiencycan be caused bymutationsin the ACADM gene. More than 54 ACADM gene mutations that cause medium-chain acyl-coenzyme A dehydrogenase deficiency have been identified.[9]Many of these mutations switch an amino acid building block in the ACADM enzyme. The most commonamino acidsubstitutionreplaceslysinewithglutamic acidat position 329 in the enzyme's chain of amino acids (also written as Lys329Glu or K329E).[10]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.[11]
References[edit]
- ^abcGRCh38: Ensembl release 89: ENSG00000117054–Ensembl,May 2017
- ^abcGRCm38: Ensembl release 89: ENSMUSG00000062908–Ensembl,May 2017
- ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "ACADM – Medium-chain specific acyl-CoA dehydrogenase, mitochondrial precursor – Homo sapiens (Human) – ACADM gene & protein".www.uniprot.org.
- ^Matsubara Y, Kraus JP, Yang-Feng TL, Francke U, Rosenberg LE, Tanaka K (Sep 1986)."Molecular cloning of cDNAs encoding rat and human medium-chain acyl-CoA dehydrogenase and assignment of the gene to human chromosome 1".Proceedings of the National Academy of Sciences of the United States of America.83(17): 6543–7.Bibcode:1986PNAS...83.6543M.doi:10.1073/pnas.83.17.6543.PMC386540.PMID3462713.
- ^Goetzman ES, Alcorn JF, Bharathi SS, Uppala R, McHugh KJ, Kosmider B, Chen R, Zuo YY, Beck ME, McKinney RW, Skilling H, Suhrie KR, Karunanidhi A, Yeasted R, Otsubo C, Ellis B, Tyurina YY, Kagan VE, Mallampalli RK, Vockley J (Apr 2014)."Long-chain acyl-CoA dehydrogenase deficiency as a cause of pulmonary surfactant dysfunction".The Journal of Biological Chemistry.289(15): 10668–79.doi:10.1074/jbc.M113.540260.PMC4036448.PMID24591516.
- ^Ezzeddini R, Taghikhani M, Salek Farrokhi A, Somi MH, Samadi N, Esfahani A, Rasaee, MJ (May 2021)."Downregulation of fatty acid oxidation by involvement of HIF-1α and PPARγ in human gastric adenocarcinoma and its related clinical significance".Journal of Physiology and Biochemistry.77(2): 249–260.doi:10.1007/s13105-021-00791-3.PMID33730333.S2CID232300877.
- ^Pagon RA, Bird TD, Dolan CR, et al. (1993). "Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency".PMID20301597.
{{cite journal}}:Cite journal requires|journal=(help) - ^Gregersen N, Andresen BS, Bross P, Winter V, Rüdiger N, Engst S, Christensen E, Kelly D, Strauss AW, Kølvraa S (Apr 1991)."Molecular characterization of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency: identification of a lys329 to glu mutation in the MCAD gene, and expression of inactive mutant enzyme protein in E. coli"(PDF).Human Genetics.86(6): 545–51.doi:10.1007/bf00201539.PMID1902818.S2CID9687627.
- ^Sturm M, Herebian D, Mueller M, Laryea MD, Spiekerkoetter U (2012)."Functional effects of different medium-chain acyl-CoA dehydrogenase genotypes and identification of asymptomatic variants".PLOS ONE.7(9): e45110.Bibcode:2012PLoSO...745110S.doi:10.1371/journal.pone.0045110.PMC3444485.PMID23028790.
Further reading[edit]
- Gregersen N, Andresen BS, Corydon MJ, Corydon TJ, Olsen RK, Bolund L, Bross P (Sep 2001)."Mutation analysis in mitochondrial fatty acid oxidation defects: Exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype-phenotype relationship".Human Mutation.18(3): 169–89.doi:10.1002/humu.1174.PMID11524729.S2CID22616789.
- Wang SS, Fernhoff PM, Hannon WH, Khoury MJ (1999)."Medium chain acyl-CoA dehydrogenase deficiency human genome epidemiology review".Genetics in Medicine.1(7): 332–9.doi:10.1097/00125817-199911000-00004.PMID11263545.
External links[edit]
- GeneReviews/NIH/NCBI/UW entry on Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency
- GeneCard
- ACADM at The GDB Human Genome Database
- HumanACADMgenome location andACADMgene details page in theUCSC Genome Browser.