Dihydrolipoyl Dehydrogenase (DLD)

LAD; GCSL; Dihydrolipoamide Dehydrogenase; E3 Component Of Pyruvate Dehydrogenase Complex; 2-Oxo-Glutarate Complex; Branched Chain Keto Acid Dehydrogenase Complex

SPN	V892
HGNC	2898
MGI	107450
PubMed	17110466
RGD	735073
UniProt	P09622
Wiki	DLD

The dihydrolipoate, still bound to a lysine residue of the complex, then migrates to the dihydrolipoyl dehydrogenase (E3) active site where it undergoes a flavin-mediated oxidation, identical in chemistry to disulfide isomerase. First, FAD oxidizes dihydrolipoate back to its lipoate resting state, producing FADH₂.

Dihydrolipoamide dehydrogenase is the L protein of the mitochondrial glycine cleavage system. The L protein, also named dihydrolipoamide dehydrogenase, is also a component of the pyruvate dehydrogenase complex, the alpha-ketoglutarate dehydrogenase complex, and the branched-chain alpha-keto acide dehydrogenase complex. Mutations in this gene have been identified in patients with E3-deficient maple syrup urine disease and lipoamide dehydrogenase deficiency.

Reference

"Isolation and sequence determination of cDNA clones for porcine and human lipoamide dehydrogenase. Homology to other disulfide oxidoreductases."
J. Biol. Chem. 262:17313-17318(1987) [PubMed] [Europe PMC] [Abstract]

"Cloning and cDNA sequence of the dihydrolipoamide dehydrogenase component human alpha-ketoacid dehydrogenase complexes."
Proc. Natl. Acad. Sci. U.S.A. 85:1422-1426(1988) [PubMed] [Europe PMC] [Abstract]

"The structure of the human dihydrolipoamide dehydrogenase gene (DLD) and its upstream elements."
Genomics 17:376-381(1993) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence of human chromosome 7."
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]

"Human chromosome 7: DNA sequence and biology."
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Characterization of the transcriptional regulatory region of the human dihydrolipoamide dehydrogenase gene."
Proc. Natl. Acad. Sci. U.S.A. 89:10964-10968(1992) [PubMed] [Europe PMC] [Abstract]

"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Resveratrol-induced changes of the human adipocyte secretion profile."
J. Proteome Res. 11:4733-4743(2012) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations."
J. Mol. Biol. 350:543-552(2005) [PubMed] [Europe PMC] [Abstract]

"How dihydrolipoamide dehydrogenase-binding protein binds dihydrolipoamide dehydrogenase in the human pyruvate dehydrogenase complex."
J. Biol. Chem. 281:648-655(2006) [PubMed] [Europe PMC] [Abstract]

"Structural insight into interactions between dihydrolipoamide dehydrogenase (E3) and E3 binding protein of human pyruvate dehydrogenase complex."
Structure 14:611-621(2006) [PubMed] [Europe PMC] [Abstract]

"Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient."
Proc. Natl. Acad. Sci. U.S.A. 90:5186-5190(1993) [PubMed] [Europe PMC] [Abstract]

"Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency."
Hum. Mol. Genet. 5:1925-1930(1996) [PubMed] [Europe PMC] [Abstract]

"Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews."
Am. J. Med. Genet. 82:177-182(1999) [PubMed] [Europe PMC] [Abstract]