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Identification
HMDB Protein ID HMDBP00054
Secondary Accession Numbers
  • 5283
  • HMDBP03598
Name Dihydrolipoyl dehydrogenase, mitochondrial
Synonyms
  1. Dihydrolipoamide dehydrogenase
  2. Glycine cleavage system L protein
Gene Name DLD
Protein Type Unknown
Biological Properties
General Function Involved in oxidoreductase activity
Specific Function Lipoamide dehydrogenase is a component of the glycine cleavage system as well as of the alpha-ketoacid dehydrogenase complexes. Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction.
Pathways
  • 2-aminoadipic 2-oxoadipic aciduria
  • 2-ketoglutarate dehydrogenase complex deficiency
  • 2-Methyl-3-Hydroxybutryl CoA Dehydrogenase Deficiency
  • 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency
  • 3-hydroxyisobutyric acid dehydrogenase deficiency
  • 3-hydroxyisobutyric aciduria
  • 3-Methylcrotonyl Coa Carboxylase Deficiency Type I
  • 3-Methylglutaconic Aciduria Type I
  • 3-Methylglutaconic Aciduria Type III
  • 3-Methylglutaconic Aciduria Type IV
  • 3-Phosphoglycerate dehydrogenase deficiency
  • Ammonia Recycling
  • Beta-Ketothiolase Deficiency
  • Citrate cycle (TCA cycle)
  • Citric Acid Cycle
  • Congenital lactic acidosis
  • Dihydropyrimidine Dehydrogenase Deficiency (DHPD)
  • Dimethylglycine Dehydrogenase Deficiency
  • Dimethylglycine Dehydrogenase Deficiency
  • Fumarase deficiency
  • Glutaminolysis and Cancer
  • Glutaric Aciduria Type I
  • Glycine and Serine Metabolism
  • Glycine, serine and threonine metabolism
  • Glycolysis / Gluconeogenesis
  • Hyperglycinemia, non-ketotic
  • Hyperlysinemia I, Familial
  • Hyperlysinemia II or Saccharopinuria
  • Isobutyryl-coa dehydrogenase deficiency
  • Isovaleric acidemia
  • Isovaleric Aciduria
  • Leigh Syndrome
  • Lysine Degradation
  • Maple Syrup Urine Disease
  • Methylmalonate Semialdehyde Dehydrogenase Deficiency
  • Methylmalonic Aciduria
  • Mitochondrial complex II deficiency
  • Non Ketotic Hyperglycinemia
  • Primary hyperoxaluria II, PH2
  • Propionic Acidemia
  • Pyridoxine dependency with seizures
  • Pyruvate Decarboxylase E1 Component Deficiency (PDHE1 Deficiency)
  • Pyruvate Dehydrogenase Complex Deficiency
  • Pyruvate dehydrogenase deficiency (E2)
  • Pyruvate dehydrogenase deficiency (E3)
  • Pyruvate kinase deficiency
  • Pyruvate Metabolism
  • Pyruvate metabolism
  • Saccharopinuria/Hyperlysinemia II
  • Sarcosinemia
  • The oncogenic action of 2-hydroxyglutarate
  • The oncogenic action of D-2-hydroxyglutarate in Hydroxygluaricaciduria
  • The Oncogenic Action of Fumarate
  • The oncogenic action of L-2-hydroxyglutarate in Hydroxygluaricaciduria
  • The Oncogenic Action of Succinate
  • Threonine and 2-Oxobutanoate Degradation
  • Valine, Leucine and Isoleucine Degradation
  • Valine, leucine and isoleucine degradation
  • Warburg Effect
Reactions
Protein N(6)-(dihydrolipoyl)lysine + NAD → protein N(6)-(lipoyl)lysine + NADH details
Dihydrolipoamide + NAD → Lipoamide + NADH + Hydrogen Ion details
Dihydrolipoylprotein + NAD → Lipoylprotein + NADH + Hydrogen Ion details
Enzyme N6-(dihydrolipoyl)lysine + NAD → Enzyme N6-(lipoyl)lysine + NADH + Hydrogen Ion details
Coenzyme A + NAD + Pyruvic acid → Carbon dioxide + Hydrogen Ion + NADH + Acetyl-CoA details
GO Classification
Biological Process
cell redox homeostasis
dihydrolipoamide metabolic process
gastrulation
lipoate metabolic process
mitochondrial electron transport, NADH to ubiquinone
regulation of acetyl-CoA biosynthetic process from pyruvate
regulation of membrane potential
sperm capacitation
branched-chain amino acid catabolic process
cellular nitrogen compound metabolic process
pyruvate metabolic process
2-oxoglutarate metabolic process
lysine catabolic process
tricarboxylic acid cycle
proteolysis
aging
acetyl-CoA biosynthetic process from pyruvate
Cellular Component
mitochondrial matrix
nucleus
flagellum
acrosomal matrix
oxoglutarate dehydrogenase complex
pyruvate dehydrogenase complex
Component
cell part
intracellular part
cytoplasm
Function
binding
catalytic activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
oxidoreductase activity
oxidoreductase activity, acting on nadh or nadph
oxidoreductase activity, acting on a sulfur group of donors, nad or nadp as acceptor
dihydrolipoyl dehydrogenase activity
fad or fadh2 binding
Molecular Function
NAD binding
flavin adenine dinucleotide binding
dihydrolipoyl dehydrogenase activity
lipoamide binding
Process
metabolic process
cellular process
oxidation reduction
cellular homeostasis
cell redox homeostasis
Cellular Location
  1. Mitochondrion matrix
Gene Properties
Chromosome Location 7
Locus 7q31-q32
SNPs DLD
Gene Sequence
>1530 bp
ATGCAGAGCTGGAGTCGTGTGTACTGCTCCTTGGCCAAGAGAGGCCATTTCAATCGAATA
TCTCATGGCCTACAGGGACTTTCTGCAGTGCCTCTGAGAACTTACGCAGATCAGCCGATT
GATGCTGATGTAACAGTTATAGGTTCTGGTCCTGGAGGATATGTTGCTGCTATTAAAGCT
GCCCAGTTAGGCTTCAAGACAGTCTGCATTGAGAAAAATGAAACACTTGGTGGAACATGC
TTGAATGTTGGTTGTATTCCTTCTAAGGCTTTATTGAACAACTCTCATTATTACCATATG
GCCCATGGAAAAGATTTTGCATCTAGAGGAATTGAAATGTCCGAAGTTCGCTTGAATTTA
GACAAGATGATGGAGCAGAAGAGTACTGCAGTAAAAGCTTTAACAGGTGGAATTGCCCAC
TTATTCAAACAGAATAAGGTTGTTCATGTCAATGGATATGGAAAGATAACTGGCAAAAAT
CAAGTCACTGCTACGAAAGCTGATGGCGGCACTCAGGTTATTGATACAAAGAACATTCTT
ATAGCCACGGGTTCAGAAGTTACTCCTTTTCCTGGAATCACGATAGATGAAGATACAATA
GTGTCATCTACAGGTGCTTTATCTTTAAAAAAAGTTCCAGAAAAGATGGTTGTTATTGGT
GCAGGAGTAATAGGTGTAGAATTGGGTTCAGTTTGGCAAAGACTTGGTGCAGATGTGACA
GCAGTTGAATTTTTAGGTCATGTAGGTGGAGTTGGAATTGATATGGAGATATCTAAAAAC
TTTCAACGCATCCTTCAAAAACAGGGGTTTAAATTTAAATTGAATACAAAGGTTACTGGT
GCTACCAAGAAGTCAGATGGAAAAATTGATGTTTCTATTGAAGCTGCTTCTGGTGGTAAA
GCTGAAGTTATCACTTGTGATGTACTCTTGGTTTGCATTGGCCGACGACCCTTTACTAAG
AATTTGGGACTAGAAGAGCTGGGAATTGAACTAGATCCCAGAGGTAGAATTCCAGTCAAT
ACCAGATTTCAAACTAAAATTCCAAATATCTATGCCATTGGTGATGTAGTTGCTGGTCCA
ATGCTGGCTCACAAAGCAGAGGATGAAGGCATTATCTGTGTTGAAGGAATGGCTGGTGGT
GCTGTGCACATTGACTACAATTGTGTGCCATCAGTGATTTACACACACCCTGAAGTTGCT
TGGGTTGGCAAATCAGAAGAGCAGTTGAAAGAAGAGGGTATTGAGTACAAAGTTGGGAAA
TTCCCATTTGCTGCTAACAGCAGAGCTAAGACAAATGCTGACACAGATGGCATGGTGAAG
ATCCTTGGGCAGAAATCGACAGACAGAGTACTGGGAGCACATATTCTTGGACCAGGTGCT
GGAGAAATGGTAAATGAAGCTGCTCTTGCTTTGGAATATGGAGCATCCTGTGAAGATATA
GCTAGAGTCTGTCATGCACATCCGACCTTATCAGAAGCTTTTAGAGAAGCAAATCTTGCT
GCGTCATTTGGCAAATCAATCAACTTTTGA
Protein Properties
Number of Residues 509
Molecular Weight 54176.91
Theoretical pI 7.855
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Dihydrolipoyl dehydrogenase, mitochondrial
MQSWSRVYCSLAKRGHFNRISHGLQGLSAVPLRTYADQPIDADVTVIGSGPGGYVAAIKA
AQLGFKTVCIEKNETLGGTCLNVGCIPSKALLNNSHYYHMAHGKDFASRGIEMSEVRLNL
DKMMEQKSTAVKALTGGIAHLFKQNKVVHVNGYGKITGKNQVTATKADGGTQVIDTKNIL
IATGSEVTPFPGITIDEDTIVSSTGALSLKKVPEKMVVIGAGVIGVELGSVWQRLGADVT
AVEFLGHVGGVGIDMEISKNFQRILQKQGFKFKLNTKVTGATKKSDGKIDVSIEAASGGK
AEVITCDVLLVCIGRRPFTKNLGLEELGIELDPRGRIPVNTRFQTKIPNIYAIGDVVAGP
MLAHKAEDEGIICVEGMAGGAVHIDYNCVPSVIYTHPEVAWVGKSEEQLKEEGIEYKVGK
FPFAANSRAKTNADTDGMVKILGQKSTDRVLGAHILGPGAGEMVNEAALALEYGASCEDI
ARVCHAHPTLSEAFREANLAASFGKSINF
GenBank ID Protein 91199540
UniProtKB/Swiss-Prot ID P09622
UniProtKB/Swiss-Prot Entry Name DLDH_HUMAN
PDB IDs
GenBank Gene ID NM_000108.3
GeneCard ID DLD
GenAtlas ID DLD
HGNC ID HGNC:2898
References
General References
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  3. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  4. Ciszak EM, Makal A, Hong YS, Vettaikkorumakankauv AK, Korotchkina LG, Patel MS: How dihydrolipoamide dehydrogenase-binding protein binds dihydrolipoamide dehydrogenase in the human pyruvate dehydrogenase complex. J Biol Chem. 2006 Jan 6;281(1):648-55. Epub 2005 Nov 1. [PubMed:16263718 ]
  5. Brautigam CA, Wynn RM, Chuang JL, Machius M, Tomchick DR, Chuang DT: Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex. Structure. 2006 Mar;14(3):611-21. Epub 2006 Jan 26. [PubMed:16442803 ]
  6. Otulakowski G, Robinson BH: Isolation and sequence determination of cDNA clones for porcine and human lipoamide dehydrogenase. Homology to other disulfide oxidoreductases. J Biol Chem. 1987 Dec 25;262(36):17313-8. [PubMed:3693355 ]
  7. Pons G, Raefsky-Estrin C, Carothers DJ, Pepin RA, Javed AA, Jesse BW, Ganapathi MK, Samols D, Patel MS: Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component human alpha-ketoacid dehydrogenase complexes. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1422-6. [PubMed:3278312 ]
  8. Feigenbaum AS, Robinson BH: The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements. Genomics. 1993 Aug;17(2):376-81. [PubMed:8406489 ]
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  10. Johanning GL, Morris JI, Madhusudhan KT, Samols D, Patel MS: Characterization of the transcriptional regulatory region of the human dihydrolipoamide dehydrogenase gene. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10964-8. [PubMed:1332063 ]
  11. Brautigam CA, Chuang JL, Tomchick DR, Machius M, Chuang DT: Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations. J Mol Biol. 2005 Jul 15;350(3):543-52. [PubMed:15946682 ]
  12. Liu TC, Kim H, Arizmendi C, Kitano A, Patel MS: Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5186-90. [PubMed:8506365 ]
  13. Hong YS, Kerr DS, Craigen WJ, Tan J, Pan Y, Lusk M, Patel MS: Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency. Hum Mol Genet. 1996 Dec;5(12):1925-30. [PubMed:8968745 ]
  14. Shaag A, Saada A, Berger I, Mandel H, Joseph A, Feigenbaum A, Elpeleg ON: Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews. Am J Med Genet. 1999 Jan 15;82(2):177-82. [PubMed:9934985 ]