MetaCyc Enzyme: pyruvate dehydrogenase E2 component

Gene: DLAT Accession Number: HS07688 (MetaCyc)

Synonyms: DLTA, 70 kDa mitochondrial autoantigen of primary biliary cirrhosis, dihydrolipoamide S-acetyltransferase component of pyruvate dehydrogenase complex, M2 antigen complex 70 kDa subunit, PDC-E2, PDCE2, pyruvate dehydrogenase complex E2 subunit, mitochondrial dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex

Species: Homo sapiens

Component of: pyruvate dehydrogenase complex (extended summary available)

The E2 component of the pyruvate dehydrogenase complex is a dihydrolipoamide acetyltransferase. About 60 copies of E2 form the inner core of the complex. The E2 component contains two lipoyl sites, which bind the substrate and interact with both the E1 and E3 components. The protein is composed of an amino-terminal lipoyl-bearing domain and a carboxy-terminal catalytic domain. The lipoyl-bearing domain contains two repeating units of 127 amino acids, each harboring one lipoate-binding lysine [Thekkumkara88].

Human cDNAs have been isolated from multiple tissues, including heart, placenta [Moehario90] and liver [Coppel88]. The human gene was mapped on chromosome 11 band q23.1 [Leung93].

Defects in the DLAT gene are the cause of pyruvate dehydrogenase E2 deficiency, also known as lactic acidemia. Pyruvate dehydrogenase deficiency is a major cause of primary lactic acidosis and neurological dysfunction in infancy and early childhood [Head05].

Locations: mitochondrion

Map Position: [113,407,680 -> 113,446,449]

Molecular Weight of Polypeptide: 68.997 kD (from nucleotide sequence)

Unification Links: ArrayExpress:P10515 , DIP:DIP-29496N , Entrez-gene:1737 , Mint:MINT-3007324 , PhosphoSite:P10515 , PhylomeDB:P10515 , Pride:P10515 , Protein Model Portal:P10515 , SMR:P10515 , String:9606.ENSP00000280346 , UniProt:P10515

Relationship Links: InterPro:IN-FAMILY:IPR000089 , InterPro:IN-FAMILY:IPR001078 , InterPro:IN-FAMILY:IPR003016 , InterPro:IN-FAMILY:IPR004167 , InterPro:IN-FAMILY:IPR006257 , InterPro:IN-FAMILY:IPR011053 , InterPro:IN-FAMILY:IPR023213 , PDB:Structure:1FYC , PDB:Structure:1Y8N , PDB:Structure:1Y8O , PDB:Structure:1Y8P , PDB:Structure:2DNE , PDB:Structure:2PNR , PDB:Structure:2Q8I , PDB:Structure:3B8K , PDB:Structure:3CRK , PDB:Structure:3CRL , 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:0006085 - acetyl-CoA biosynthetic process
GO:0006096 - glycolytic process
GO:0006418 - tRNA aminoacylation for protein translation
GO:0008152 - metabolic process
Molecular Function: GO:0004742 - dihydrolipoyllysine-residue acetyltransferase activity
GO:0004812 - aminoacyl-tRNA ligase activity
GO:0005515 - protein binding
GO:0005524 - ATP binding
GO:0016740 - transferase activity
GO:0016746 - transferase activity, transferring acyl groups
Cellular Component: GO:0005739 - mitochondrion
GO:0005967 - mitochondrial pyruvate dehydrogenase complex

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

Enzymatic reaction of: dihydrolipoyllysine-residue acetyltransferase (pyruvate dehydrogenase E2 component)

EC Number:

acetyl-CoA + a [pyruvate dehydrogenase E2 protein] N6-dihydrolipoyl-L-lysine <=> a [pyruvate dehydrogenase E2 protein] N6-S-acetyldihydrolipoyl-L-lysine + coenzyme A

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

This reaction is reversible.

In Pathways: pyruvate decarboxylation to acetyl CoA

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

Cofactors or Prosthetic Groups: (R)-lipoate [Howard98]

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

EC Number: 1.2.1.-

pyruvate + coenzyme A + NAD+ <=> acetyl-CoA + CO2 + NADH

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


Schematic showing introns, exons and/or isoforms of DLAT


Coppel88: Coppel RL, McNeilage LJ, Surh CD, Van de Water J, Spithill TW, Whittingham S, Gershwin ME (1988). "Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: dihydrolipoamide acetyltransferase." Proc Natl Acad Sci U S A 85(19);7317-21. PMID: 3174635

Head05: Head RA, Brown RM, Zolkipli Z, Shahdadpuri R, King MD, Clayton PT, Brown GK (2005). "Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency." Ann Neurol 58(2);234-41. PMID: 16049940

Howard98: Howard MJ, Fuller C, Broadhurst RW, Perham RN, Tang JG, Quinn J, Diamond AG, Yeaman SJ (1998). "Three-dimensional structure of the major autoantigen in primary biliary cirrhosis." Gastroenterology 115(1);139-46. PMID: 9649469

Leung93: Leung PS, Watanabe Y, Munoz S, Teuber SS, Patel MS, Korenberg JR, Hara P, Coppel R, Gershwin ME (1993). "Chromosome localization and RFLP analysis of PDC-E2: the major autoantigen of primary biliary cirrhosis." Autoimmunity 14(4);335-40. PMID: 8102256

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

Moehario90: Moehario LH, Smooker PM, Devenish RJ, Mackay IR, Gershwin ME, Marzuki S (1990). "Nucleotide sequence of a cDNA encoding the lipoate acetyl transferase (E2) of human heart pyruvate dehydrogenase complex differs from that of human placenta." Biochem Int 20(2);417-22. PMID: 2317220

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

Thekkumkara88: Thekkumkara TJ, Ho L, Wexler ID, Pons G, Liu TC, Patel MS (1988). "Nucleotide sequence of a cDNA for the dihydrolipoamide acetyltransferase component of human pyruvate dehydrogenase complex." FEBS Lett 240(1-2);45-8. PMID: 3191998

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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