|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)
|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
|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
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].
Enzymatic reaction of: pyruvate dehydrogenase
EC Number: 1.2.1.-
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.
This reaction is reversible.
In Pathways: pyruvate decarboxylation to acetyl CoA
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
©2014 SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025-3493