Hmdb loader
Identification
HMDB Protein ID HMDBP00202
Secondary Accession Numbers
  • 5434
Name Glutaryl-CoA dehydrogenase, mitochondrial
Synonyms
  1. GCD
Gene Name GCDH
Protein Type Unknown
Biological Properties
General Function Involved in acyl-CoA dehydrogenase activity
Specific Function Catalyzes the oxidative decarboxylation of glutaryl-CoA to crotonyl-CoA and CO(2) in the degradative pathway of L-lysine, L-hydroxylysine, and L-tryptophan metabolism. It uses electron transfer flavoprotein as its electron acceptor. Isoform Short is inactive.
Pathways
  • 2-aminoadipic 2-oxoadipic aciduria
  • Carnitine palmitoyl transferase deficiency (I)
  • Carnitine palmitoyl transferase deficiency (II)
  • Ethylmalonic Encephalopathy
  • Fatty acid Metabolism
  • fatty acid metabolism
  • Glutaric Aciduria Type I
  • Glutaric Aciduria Type I
  • Hyperlysinemia I, Familial
  • Hyperlysinemia II or Saccharopinuria
  • Long chain acyl-CoA dehydrogenase deficiency (LCAD)
  • Lysine degradation
  • Lysine degradation
  • Medium chain acyl-coa dehydrogenase deficiency (MCAD)
  • Pyridoxine dependency with seizures
  • Saccharopinuria/Hyperlysinemia II
  • Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency)
  • Trifunctional protein deficiency
  • Tryptophan metabolism
  • Very-long-chain acyl coa dehydrogenase deficiency (VLCAD)
Reactions
Glutaryl-CoA + electron-transfer flavoprotein → Crotonoyl-CoA + CO(2) + reduced electron-transfer flavoprotein details
Glutaryl-CoA + FAD → FADH + Crotonoyl-CoA + Carbon dioxide details
Glutaryl-CoA + Electron-transferring flavoprotein → Crotonoyl-CoA + Reduced electron-transferring flavoprotein + Carbon dioxide details
Glutaryl-CoA + Electron-transferring flavoprotein → Glutaconyl-CoA + Reduced electron-transferring flavoprotein details
GO Classification
Biological Process
cellular nitrogen compound metabolic process
lysine catabolic process
fatty acid oxidation
fatty-acyl-CoA biosynthetic process
tryptophan metabolic process
Cellular Component
mitochondrial matrix
mitochondrial inner membrane
Function
oxidoreductase activity, acting on the ch-ch group of donors
acyl-coa dehydrogenase activity
binding
catalytic activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
oxidoreductase activity
fad or fadh2 binding
Molecular Function
glutaryl-CoA dehydrogenase activity
flavin adenine dinucleotide binding
fatty-acyl-CoA binding
Process
metabolic process
oxidation reduction
Cellular Location
  1. Mitochondrion matrix
Gene Properties
Chromosome Location 19
Locus 19p13.2
SNPs GCDH
Gene Sequence
>1317 bp
ATGGCCCTGAGAGGCGTCTCCGTGCGGCTGCTGAGCCGCGGACCCGGCCTGCACGTCCTT
CGCACGTGGGTCTCGTCGGCGGCGCAGACCGAGAAAGGCGGGAGAACACAGAGCCAACTG
GCTAAGTCCTCGCGTCCCGAGTTTGACTGGCAGGACCCGCTGGTGCTGGAGGAGCAGCTG
ACCACAGATGAGATCCTCATCAGGGACACCTTCCGCACCTACTGCCAGGAGAGACTCATG
CCTCGCATCCTGTTGGCCAATCGCAACGAAGTTTTTCATCGGGAGATCATTTCGGAGATG
GGGGAGTTGGGTGTGCTGGGCCCCACCATCAAAGGATATGGCTGTGCTGGGGTTTCGTCT
GTGGCCTATGGGCTCCTGGCCCGAGAGCTGGAGCGGGTGGACAGTGGCTACAGGTCGGCG
ATGAGTGTCCAGTCCTCCCTCGTCATGCACCCTATCTATGCCTATGGCAGCGAGGAACAG
CGGCAGAAGTACCTGCCCCAGCTGGCCAAGGGGGAGCTCCTGGGCTGCTTCGGGCTCACA
GAGCCCAACAGCGGAAGTGACCCCAGCAGCATGGAGACCAGAGCCCACTACAACTCATCC
AACAAGAGCTACACCCTCAATGGGACCAAGACCTGGATCACGAACTCGCCTATGGCCGAT
CTGTTTGTAGTGTGGGCTCGGTGTGAAGATGGCTGCATTCGGGGCTTCCTGCTGGAGAAG
GGGATGCGGGGTCTCTCGGCCCCCAGGATCCAGGGCAAGTTCTCGCTGCGGGCCTCAGCC
ACAGGCATGATCATCATGGACGGTGTGGAGGTGCCAGAGGAGAATGTGCTCCCTGGTGCA
TCCAGCCTGGGGGGTCCCTTCGGCTGCCTGAACAACGCCCGGTACGGCATCGCGTGGGGC
GTGCTTGGAGCTTCGGAGTTCTGCTTGCACACAGCCCGGCAGTACGCCCTCGACAGGATG
CAGTTTGGTGTCCCACTGGCCAGGAACCAGCTGATTCAGAAGAAGCTGGCAGACATGCTC
ACTGAGATTACCCTGGGCCTTCACGCCTGCCTGCAGCTCGGCCGCTTGAAGGACCAGGAC
AAGGCTGCCCCCGAGATGGTTTCTCTGCTGAAGAGGAATAACTGTGGGAAAGCCCTGGAC
ATCGCCCGCCAGGCCCGAGACATGCTGGGGGGGAATGGGATTTCTGACGAGTATCACGTG
ATCCGGCACGCCATGAACCTGGAGGCCGTGAACACCTACGAAGGTACACATGACATTCAC
GCCCTGATCCTTGGGAGAGCTATCACGGGAATCCAGGCGTTCACGGCCAGCAAGTGA
Protein Properties
Number of Residues 438
Molecular Weight 48126.715
Theoretical pI 8.062
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Glutaryl-CoA dehydrogenase, mitochondrial
MALRGVSVRLLSRGPGLHVLRTWVSSAAQTEKGGRTQSQLAKSSRPEFDWQDPLVLEEQL
TTDEILIRDTFRTYCQERLMPRILLANRNEVFHREIISEMGELGVLGPTIKGYGCAGVSS
VAYGLLARELERVDSGYRSAMSVQSSLVMHPIYAYGSEEQRQKYLPQLAKGELLGCFGLT
EPNSGSDPSSMETRAHYNSSNKSYTLNGTKTWITNSPMADLFVVWARCEDGCIRGFLLEK
GMRGLSAPRIQGKFSLRASATGMIIMDGVEVPEENVLPGASSLGGPFGCLNNARYGIAWG
VLGASEFCLHTARQYALDRMQFGVPLARNQLIQKKLADMLTEITLGLHACLQLGRLKDQD
KAAPEMVSLLKRNNCGKALDIARQARDMLGGNGISDEYHVIRHAMNLEAVNTYEGTHDIH
ALILGRAITGIQAFTASK
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q92947
UniProtKB/Swiss-Prot Entry Name GCDH_HUMAN
PDB IDs
GenBank Gene ID U69141
GeneCard ID GCDH
GenAtlas ID GCDH
HGNC ID HGNC:4189
References
General References
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  4. Goodman SI, Kratz LE, Frerman FE: Pork and human cDNAs encoding glutaryl-CoA dehydrogenase. Prog Clin Biol Res. 1992;375:169-73. [PubMed:1438360 ]
  5. Goodman SI, Kratz LE, DiGiulio KA, Biery BJ, Goodman KE, Isaya G, Frerman FE: Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli. Hum Mol Genet. 1995 Sep;4(9):1493-8. [PubMed:8541831 ]
  6. Schwartz M, Christensen E, Superti-Furga A, Brandt NJ: The human glutaryl-CoA dehydrogenase gene: report of intronic sequences and of 13 novel mutations causing glutaric aciduria type I. Hum Genet. 1998 Apr;102(4):452-8. [PubMed:9600243 ]
  7. Goodman SI, Stein DE, Schlesinger S, Christensen E, Schwartz M, Greenberg CR, Elpeleg ON: Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): review and report of thirty novel mutations. Hum Mutat. 1998;12(3):141-4. [PubMed:9711871 ]
  8. Fu Z, Wang M, Paschke R, Rao KS, Frerman FE, Kim JJ: Crystal structures of human glutaryl-CoA dehydrogenase with and without an alternate substrate: structural bases of dehydrogenation and decarboxylation reactions. Biochemistry. 2004 Aug 3;43(30):9674-84. [PubMed:15274622 ]
  9. Rao KS, Fu Z, Albro M, Narayanan B, Baddam S, Lee HJ, Kim JJ, Frerman FE: The effect of a Glu370Asp mutation in glutaryl-CoA dehydrogenase on proton transfer to the dienolate intermediate. Biochemistry. 2007 Dec 18;46(50):14468-77. Epub 2007 Nov 17. [PubMed:18020372 ]
  10. Biery BJ, Stein DE, Morton DH, Goodman SI: Gene structure and mutations of glutaryl-coenzyme A dehydrogenase: impaired association of enzyme subunits that is due to an A421V substitution causes glutaric acidemia type I in the Amish. Am J Hum Genet. 1996 Nov;59(5):1006-11. [PubMed:8900227 ]
  11. Anikster Y, Shaag A, Joseph A, Mandel H, Ben-Zeev B, Christensen E, Elpeleg ON: Glutaric aciduria type I in the Arab and Jewish communities in Israel. Am J Hum Genet. 1996 Nov;59(5):1012-8. [PubMed:8900228 ]
  12. Muhlhausen C, Christensen E, Schwartz M, Muschol N, Ullrich K, Lukacs Z: Severe phenotype despite high residual glutaryl-CoA dehydrogenase activity: a novel mutation in a Turkish patient with glutaric aciduria type I. J Inherit Metab Dis. 2003;26(7):713-4. [PubMed:14707522 ]
  13. Keyser B, Muhlhausen C, Dickmanns A, Christensen E, Muschol N, Ullrich K, Braulke T: Disease-causing missense mutations affect enzymatic activity, stability and oligomerization of glutaryl-CoA dehydrogenase (GCDH). Hum Mol Genet. 2008 Dec 15;17(24):3854-63. doi: 10.1093/hmg/ddn284. Epub 2008 Sep 5. [PubMed:18775954 ]