Medium-chain specific acyl-CoA dehydrogenase, mitochondrial

Details

Name
Medium-chain specific acyl-CoA dehydrogenase, mitochondrial
Synonyms
  • 1.3.8.7
  • MCAD
Gene Name
ACADM
Organism
Humans
Amino acid sequence
>lcl|BSEQ0003460|Medium-chain specific acyl-CoA dehydrogenase, mitochondrial
MAAGFGRCCRVLRSISRFHWRSQHTKANRQREPGLGFSFEFTEQQKEFQATARKFAREEI
IPVAAEYDKTGEYPVPLIRRAWELGLMNTHIPENCGGLGLGTFDACLISEELAYGCTGVQ
TAIEGNSLGQMPIIIAGNDQQKKKYLGRMTEEPLMCAYCVTEPGAGSDVAGIKTKAEKKG
DEYIINGQKMWITNGGKANWYFLLARSDPDPKAPANKAFTGFIVEADTPGIQIGRKELNM
GQRCSDTRGIVFEDVKVPKENVLIGDGAGFKVAMGAFDKTRPVVAAGAVGLAQRALDEAT
KYALERKTFGKLLVEHQAISFMLAEMAMKVELARMSYQRAAWEVDSGRRNTYYASIAKAF
AGDIANQLATDAVQILGGNGFNTEYPVEKLMRDAKIYQIYEGTSQIQRLIVAREHIDKYK
N
Number of residues
421
Molecular Weight
46587.98
Theoretical pI
8.51
GO Classification
Functions
acyl-CoA dehydrogenase activity / electron carrier activity / fatty-acyl-CoA binding / flavin adenine dinucleotide binding / identical protein binding / medium-chain-acyl-CoA dehydrogenase activity / oxidoreductase activity, acting on the CH-CH group of donors, with a flavin as acceptor
Processes
carnitine biosynthetic process / carnitine metabolic process, CoA-linked / cellular lipid metabolic process / fatty acid beta-oxidation / fatty acid beta-oxidation using acyl-CoA dehydrogenase / lipid homeostasis / medium-chain fatty acid catabolic process / medium-chain fatty acid metabolic process / oxidation-reduction process / small molecule metabolic process
Components
axon / extracellular exosome / mitochondrial matrix / mitochondrion / nucleus
General Function
Oxidoreductase activity, acting on the ch-ch group of donors, with a flavin as acceptor
Specific Function
Acyl-CoA dehydrogenase specific for acyl chain lengths of 4 to 16 that catalyzes the initial step of fatty acid beta-oxidation. Utilizes the electron transfer flavoprotein (ETF) as an electron acceptor to transfer electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion matrix
Gene sequence
>lcl|BSEQ0021302|Medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM)
ATGGCAGCGGGGTTCGGGCGATGCTGCAGGGTCCTGAGAAGTATTTCTCGTTTTCATTGG
AGATCACAGCATACAAAAGCCAATCGACAACGTGAACCAGGATTAGGATTTAGTTTTGAG
TTCACCGAACAGCAGAAAGAATTTCAAGCTACTGCTCGTAAATTTGCCAGAGAGGAAATC
ATCCCAGTGGCTGCAGAATATGATAAAACTGGTGAATATCCAGTCCCCCTAATTAGAAGA
GCCTGGGAACTTGGTTTAATGAACACACACATTCCAGAGAACTGTGGAGGTCTTGGACTT
GGAACTTTTGATGCTTGTTTAATTAGTGAAGAATTGGCTTATGGATGTACAGGGGTTCAG
ACTGCTATTGAAGGAAATTCTTTGGGGCAAATGCCTATTATTATTGCTGGAAATGATCAA
CAAAAGAAGAAGTATTTGGGGAGAATGACTGAGGAGCCATTGATGTGTGCTTATTGTGTA
ACAGAACCTGGAGCAGGCTCTGATGTAGCTGGTATAAAGACCAAAGCAGAAAAGAAAGGA
GATGAGTATATTATTAATGGTCAGAAGATGTGGATAACCAACGGAGGAAAAGCTAATTGG
TATTTTTTATTGGCACGTTCTGATCCAGATCCTAAAGCTCCTGCTAATAAAGCCTTTACT
GGATTCATTGTGGAAGCAGATACCCCAGGAATTCAGATTGGGAGAAAGGAATTAAACATG
GGCCAGCGATGTTCAGATACTAGAGGAATTGTCTTCGAAGATGTGAAAGTGCCTAAAGAA
AATGTTTTAATTGGTGACGGAGCTGGTTTCAAAGTTGCAATGGGAGCTTTTGATAAAACC
AGACCTGTAGTAGCTGCTGGTGCTGTTGGATTAGCACAAAGAGCTTTGGATGAAGCTACC
AAGTATGCCCTGGAAAGGAAAACTTTCGGAAAGCTACTTGTAGAGCACCAAGCAATATCA
TTTATGCTGGCTGAAATGGCAATGAAAGTTGAACTAGCTAGAATGAGTTACCAGAGAGCA
GCTTGGGAGGTTGATTCTGGTCGTCGAAATACCTATTATGCTTCTATTGCAAAGGCATTT
GCTGGAGATATTGCAAATCAGTTAGCTACTGATGCTGTGCAGATACTTGGAGGCAATGGA
TTTAATACAGAATATCCTGTAGAAAAACTAATGAGGGATGCCAAAATCTATCAGATTTAT
GAAGGTACTTCACAAATTCAAAGACTTATTGTAGCCCGTGAACACATTGACAAGTACAAA
AATTAA
Chromosome Location
1
Locus
1p31
External Identifiers
ResourceLink
UniProtKB IDP11310
UniProtKB Entry NameACADM_HUMAN
GenBank Protein ID187433
GenBank Gene IDM91432
GenAtlas IDACADM
HGNC IDHGNC:89
General References
  1. Kelly DP, Kim JJ, Billadello JJ, Hainline BE, Chu TW, Strauss AW: Nucleotide sequence of medium-chain acyl-CoA dehydrogenase mRNA and its expression in enzyme-deficient human tissue. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4068-72. [Article]
  2. Zhang ZF, Kelly DP, Kim JJ, Zhou YQ, Ogden ML, Whelan AJ, Strauss AW: Structural organization and regulatory regions of the human medium-chain acyl-CoA dehydrogenase gene. Biochemistry. 1992 Jan 14;31(1):81-9. [Article]
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  6. Matsubara Y, Narisawa K, Miyabayashi S, Tada K, Coates PM, Bachmann C, Elsas LJ 2nd, Pollitt RJ, Rhead WJ, Roe CR: Identification of a common mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency. Biochem Biophys Res Commun. 1990 Aug 31;171(1):498-505. [Article]
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  13. Lee HJ, Wang M, Paschke R, Nandy A, Ghisla S, Kim JJ: Crystal structures of the wild type and the Glu376Gly/Thr255Glu mutant of human medium-chain acyl-CoA dehydrogenase: influence of the location of the catalytic base on substrate specificity. Biochemistry. 1996 Sep 24;35(38):12412-20. [Article]
  14. Toogood HS, van Thiel A, Basran J, Sutcliffe MJ, Scrutton NS, Leys D: Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex. J Biol Chem. 2004 Jul 30;279(31):32904-12. Epub 2004 May 24. [Article]
  15. Toogood HS, van Thiel A, Scrutton NS, Leys D: Stabilization of non-productive conformations underpins rapid electron transfer to electron-transferring flavoprotein. J Biol Chem. 2005 Aug 26;280(34):30361-6. Epub 2005 Jun 23. [Article]
  16. Tanaka K, Yokota I, Coates PM, Strauss AW, Kelly DP, Zhang Z, Gregersen N, Andresen BS, Matsubara Y, Curtis D, et al.: Mutations in the medium chain acyl-CoA dehydrogenase (MCAD) gene. Hum Mutat. 1992;1(4):271-9. [Article]
  17. Yokota I, Indo Y, Coates PM, Tanaka K: Molecular basis of medium chain acyl-coenzyme A dehydrogenase deficiency. An A to G transition at position 985 that causes a lysine-304 to glutamate substitution in the mature protein is the single prevalent mutation. J Clin Invest. 1990 Sep;86(3):1000-3. [Article]
  18. Kelly DP, Whelan AJ, Ogden ML, Alpers R, Zhang ZF, Bellus G, Gregersen N, Dorland L, Strauss AW: Molecular characterization of inherited medium-chain acyl-CoA dehydrogenase deficiency. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9236-40. [Article]
  19. Yokota I, Coates PM, Hale DE, Rinaldo P, Tanaka K: Molecular survey of a prevalent mutation, 985A-to-G transition, and identification of five infrequent mutations in the medium-chain Acyl-CoA dehydrogenase (MCAD) gene in 55 patients with MCAD deficiency. Am J Hum Genet. 1991 Dec;49(6):1280-91. [Article]
  20. Gregersen N, Andresen BS, Bross P, Winter V, Rudiger N, Engst S, Christensen E, Kelly D, Strauss AW, Kolvraa S, et al.: 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. Hum Genet. 1991 Apr;86(6):545-51. [Article]
  21. Blakemore AI, Singleton H, Pollitt RJ, Engel PC, Kolvraa S, Gregersen N, Curtis D: Frequency of the G985 MCAD mutation in the general population. Lancet. 1991 Feb 2;337(8736):298-9. [Article]
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  23. Ziadeh R, Hoffman EP, Finegold DN, Hoop RC, Brackett JC, Strauss AW, Naylor EW: Medium chain acyl-CoA dehydrogenase deficiency in Pennsylvania: neonatal screening shows high incidence and unexpected mutation frequencies. Pediatr Res. 1995 May;37(5):675-8. [Article]
  24. Brackett JC, Sims HF, Steiner RD, Nunge M, Zimmerman EM, deMartinville B, Rinaldo P, Slaugh R, Strauss AW: A novel mutation in medium chain acyl-CoA dehydrogenase causes sudden neonatal death. J Clin Invest. 1994 Oct;94(4):1477-83. [Article]
  25. Andresen BS, Bross P, Udvari S, Kirk J, Gray G, Kmoch S, Chamoles N, Knudsen I, Winter V, Wilcken B, Yokota I, Hart K, Packman S, Harpey JP, Saudubray JM, Hale DE, Bolund L, Kolvraa S, Gregersen N: The molecular basis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in compound heterozygous patients: is there correlation between genotype and phenotype? Hum Mol Genet. 1997 May;6(5):695-707. [Article]
  26. Kuchler B, Abdel-Ghany AG, Bross P, Nandy A, Rasched I, Ghisla S: Biochemical characterization of a variant human medium-chain acyl-CoA dehydrogenase with a disease-associated mutation localized in the active site. Biochem J. 1999 Jan 15;337 ( Pt 2):225-30. [Article]
  27. Yang BZ, Ding JH, Zhou C, Dimachkie MM, Sweetman L, Dasouki MJ, Wilkinson J, Roe CR: Identification of a novel mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency. Mol Genet Metab. 2000 Mar;69(3):259-62. [Article]
  28. Andresen BS, Dobrowolski SF, O'Reilly L, Muenzer J, McCandless SE, Frazier DM, Udvari S, Bross P, Knudsen I, Banas R, Chace DH, Engel P, Naylor EW, Gregersen N: Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency. Am J Hum Genet. 2001 Jun;68(6):1408-18. Epub 2001 May 8. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02910Octanoyl-Coenzyme AexperimentalunknownDetails
DB03147Flavin adenine dinucleotideapprovedunknownDetails
DB034153-thiaoctanoyl-CoAexperimentalunknownDetails