MetaCyc Protein: pyruvate dehydrogenase E3-binding protein

Gene: PDHX Accession Number: HS03310 (MetaCyc)

Synonyms: PDX1, dihydrolipoamide dehydrogenase-binding protein of pyruvate dehydrogenase complex, E3-binding protein, E3BP, lipoyl-containing pyruvate dehydrogenase complex component X, proX

Species: Homo sapiens

Component of: pyruvate dehydrogenase complex (extended summary available)

Subunit composition of pyruvate dehydrogenase E3-binding protein = [PDHX]
         pyruvate dehydrogenase protein E3 component, mitochondrial = PDHX

Citations: [Andersson96, Yu97, Harris97, Ling98, Murray02]

Locations: mitochondrion

Map Position: [35,616,188 -> 35,695,692]

Unification Links: ArrayExpress:O00330, DIP:DIP-29026N, Ensembl:ENSG00000110435, Entrez-gene:8050, Entrez-Nucleotide:AF001437, Entrez-Nucleotide:BC010389, Entrez-Nucleotide:U79296, Entrez-Nucleotide:U82328, Entrez:AAB50223, Entrez:AAB66315, Entrez:AAC39661, Entrez:AAH10389, Entrez:CAA73606, Entrez:CAC12641, Entrez:CAC18649, GeneCards:PDX1, Mint:MINT-1482590, OMIM:245349, PhosphoSite:O00330, PhylomeDB:O00330, Pride:O00330, Protein Model Portal:O00330, RefSeq:NM_003477, RefSeq:NP_003468, SMR:O00330, String:9606.ENSP00000227868, UCSC Human Genome:NM_003477, UniGene:351622, UniProt:O00330

Relationship Links: InterPro:IN-FAMILY:IPR000089, InterPro:IN-FAMILY:IPR001078, InterPro:IN-FAMILY:IPR003016, InterPro:IN-FAMILY:IPR004167, InterPro:IN-FAMILY:IPR011053, InterPro:IN-FAMILY:IPR023213, PDB:Structure:1ZY8, PDB:Structure:2DNC, PDB:Structure:2F5Z, PDB:Structure:2F60, Pfam:IN-FAMILY:PF00198, Pfam:IN-FAMILY:PF00364, Pfam:IN-FAMILY:PF02817, Prosite:IN-FAMILY:PS00189, Prosite:IN-FAMILY:PS50968

Gene-Reaction Schematic

Gene-Reaction Schematic

GO Terms:
Biological Process:
GO:0008152 - metabolic process []
Molecular Function:
GO:0005515 - protein binding []
GO:0016746 - transferase activity, transferring acyl groups []
Cellular Component:
GO:0005739 - mitochondrion []
GO:0005967 - mitochondrial pyruvate dehydrogenase complex []

Created in HumanCyc 04-Nov-2011 by Caspi R, SRI International
Imported from HumanCyc 04-Nov-2011 by Caspi R, SRI International

Subunit of: pyruvate dehydrogenase complex

Species: Homo sapiens

Subunit composition of pyruvate dehydrogenase complex = [(PDHB)2(PDHA1)2]30[DLAT]60[(PDHX)][(DLD)2]6
         pyruvate dehydrogenase E1 component (somatic) = (PDHB)2(PDHA1)2 (summary available)
                 pyruvate dehydrogenase E1 component β subunit = PDHB (summary available)
                 pyruvate dehydrogenase E1 component α subunit (somatic) = PDHA1 (summary available)
         pyruvate dehydrogenase E2 component = DLAT (extended summary available)
         pyruvate dehydrogenase E3-binding protein = (PDHX)
                 pyruvate dehydrogenase protein E3 component, mitochondrial = PDHX
         dihydrolipoyl dehydrogenase = (DLD)2 (extended summary available)
                 dihydrolipoyl dehydrogenase monomer = DLD

The pyruvate dehydrogenase complex (PDH) is a large enzyme complex made up of multiple copies of three enzymes: E1 (20-30 copies of pyruvate dehydrogenase, an α2β2 heterotetramer), 60 copies of E2 (dihydrolipoamide acetyltransferase), and six homodimers of E3 (dihydrolipoamide dehydrogenase), together with the E3 binding protein, which is involved in the interaction between the E2 and E3 subunits.

Within the PDH complex, the E2 subunit forms the structural core and accepts acetyl groups from E1 and transfers them to coenzyme A. The irreversible decarboxylation of pyruvate and its conversion to acetyl-CoA by the PDH complex precedes the entry of glucose carbon into the tricarboxylic acid (TCA) cycle. This process is fundamental to the aerobic oxidation of glucose and is of particular importance in the brain where it is the obligatory pathway for energy generation under normal conditions [McWilliam10].

The mitochondrial pyruvate dehydrogenase complex (PDC) plays a critical fuel selection role in determining whether glucose-linked substrates are converted to acetyl-CoA. When carbohydrate stores are reduced, mammalian PDC activity is down-regulated and limits the oxidative utilization of glucose in most non-neural tissues.

Four pyruvate dehydrogenase kinase (PDK) isozymes and two pyruvate dehydrogenase phosphatase (PDP) isoforms control the activity state of PDC by determining the proportion of the pyruvate dehydrogenase (E1) component that is in the active, nonphosphorylated state [Roche03].

Created in HumanCyc 04-Nov-2011 by Caspi R, SRI International
Imported from HumanCyc 04-Nov-2011 by Caspi R, SRI International

Enzymatic reaction of: pyruvate dehydrogenase

Inferred from experiment

EC Number: 1.2.1.-

pyruvate + coenzyme A + NAD+ ⇄ acetyl-CoA + CO2 + NADH

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the direction in which it was curated.

This reaction is reversible.

In Pathways: pyruvate decarboxylation to acetyl CoA


Schematic showing introns, exons and/or isoforms of PDHX


Andersson96: Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (1996). "A "double adaptor" method for improved shotgun library construction." Anal Biochem 236(1);107-13. PMID: 8619474

Harris97: Harris RA, Bowker-Kinley MM, Wu P, Jeng J, Popov KM (1997). "Dihydrolipoamide dehydrogenase-binding protein of the human pyruvate dehydrogenase complex. DNA-derived amino acid sequence, expression, and reconstitution of the pyruvate dehydrogenase complex." J Biol Chem 272(32);19746-51. PMID: 9242632

Ling98: Ling M, McEachern G, Seyda A, MacKay N, Scherer SW, Bratinova S, Beatty B, Giovannucci-Uzielli ML, Robinson BH (1998). "Detection of a homozygous four base pair deletion in the protein X gene in a case of pyruvate dehydrogenase complex deficiency." Hum Mol Genet 7(3);501-5. PMID: 9467010

McWilliam10: McWilliam CA, Ridout CK, Brown RM, McWilliam RC, Tolmie J, Brown GK (2010). "Pyruvate dehydrogenase E2 deficiency: a potentially treatable cause of episodic dystonia." Eur J Paediatr Neurol 14(4);349-53. PMID: 20022530

Murray02: Murray J, Gilkerson R, Capaldi RA (2002). "Quantitative proteomics: the copy number of pyruvate dehydrogenase is more than 10(2)-fold lower than that of complex III in human mitochondria." FEBS Lett 529(2-3);173-8. PMID: 12372595

Roche03: Roche TE, Hiromasa Y, Turkan A, Gong X, Peng T, Yan X, Kasten SA, Bao H, Dong J (2003). "Essential roles of lipoyl domains in the activated function and control of pyruvate dehydrogenase kinases and phosphatase isoform 1." Eur J Biochem 270(6);1050-6. PMID: 12631265

Yu97: Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (1997). "Large-scale concatenation cDNA sequencing." Genome Res 7(4);353-8. PMID: 9110174

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Sat Nov 28, 2015, biocyc13.