ACADM

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.

ACADM
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesACADM, acyl-CoA dehydrogenase, C-4 to C-12 straight chain, ACAD1, MCAD, MCADH, acyl-CoA dehydrogenase medium chain
External IDsOMIM: 607008 MGI: 87867 HomoloGene: 3 GeneCards: ACADM
Gene location (Human)
Chr.Chromosome 1 (human)[1]
Band1p31.1Start75,724,347 bp[1]
End75,787,575 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

34

11364

Ensembl

ENSG00000117054

ENSMUSG00000062908

UniProt

P11310

P45952

RefSeq (mRNA)

NM_000016
NM_001127328
NM_001286042
NM_001286043
NM_001286044

NM_007382

RefSeq (protein)

NP_000007
NP_001120800
NP_001272971
NP_001272972
NP_001272973

NP_031408

Location (UCSC)Chr 1: 75.72 – 75.79 MbChr 3: 153.92 – 153.94 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.

The ACADM gene is located on the short (p) arm of chromosome 1 at position 31, from base pair 75,902,302 to base pair 75,941,203.

Structure

The protein encoded by the ACADM gene is ~47 kDa in size, and composed of 421 amino acids.[5]

Function

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]

Clinical significance

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.[8] 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 329 in the enzyme's chain of amino acids (also written as Lys329Glu or K329E).[9] 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.[10]

References
  1. GRCh38: Ensembl release 89: ENSG00000117054 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000062908 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. https://www.uniprot.org/uniprot/P11310
  6. 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. doi:10.1073/pnas.83.17.6543. PMC 386540. PMID 3462713.
  7. 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. PMC 4036448. PMID 24591516.
  8. Pagon RA, Bird TD, Dolan CR, et al. (1993). "Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency". PMID 20301597. Cite journal requires |journal= (help)
  9. 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. PMID 1902818. S2CID 9687627.
  10. 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. doi:10.1371/journal.pone.0045110. PMC 3444485. PMID 23028790.

Further reading
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