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discounted EARLY registration ends Dec 31, 2014
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Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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MetaCyc Polypeptide: pyruvate dehydrogenase E1 component β subunit

Gene: PDHB Accession Number: HS09727 (MetaCyc)

Synonyms: PHE1B, PDHE1-B

Species: Homo sapiens

Component of:
pyruvate dehydrogenase E1 component (testis)
pyruvate dehydrogenase E1 component (somatic) (summary available)
pyruvate dehydrogenase complex (extended summary available)

Summary:
cDNA clones encoding the β-subunit of the pyruvate dehydrogenase (E1) component of the human pyruvate dehydrogenase complex were isolated from multiple sources and sequenced [Ho88, Koike88, Ho90, Chun90, Huh90].

The PDHB gene encoding the enzyme was localized on chromosome 3 [Chun90] and is composed of 10 exons and 9 introns [Koike90].

Mutations in the gene can cause pyruvate dehydrogenase deficiency [Brown04].

Locations: mitochondrion

Map Position: [57,782,043 <- 57,788,240]

Molecular Weight of Polypeptide: 39.233 kD (from nucleotide sequence)

Unification Links: ArrayExpress:P11177 , DIP:DIP-37651N , Entrez-gene:5162 , Mint:MINT-3007546 , PhosphoSite:P11177 , PhylomeDB:P11177 , Pride:P11177 , Protein Model Portal:P11177 , SMR:P11177 , String:9606.ENSP00000307241 , UniProt:P11177

Relationship Links: InterPro:IN-FAMILY:IPR005475 , InterPro:IN-FAMILY:IPR005476 , InterPro:IN-FAMILY:IPR009014 , Panther:IN-FAMILY:PTHR11624:SF11 , PDB:Structure:1NI4 , PDB:Structure:2OZL , PDB:Structure:3EXE , PDB:Structure:3EXF , PDB:Structure:3EXG , PDB:Structure:3EXH , PDB:Structure:3EXI , Pfam:IN-FAMILY:PF02779 , Pfam:IN-FAMILY:PF02780 , Smart:IN-FAMILY:SM00861

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0006006 - glucose metabolic process
GO:0006096 - glycolytic process
GO:0006099 - tricarboxylic acid cycle
Molecular Function: GO:0004739 - pyruvate dehydrogenase (acetyl-transferring) activity
GO:0016491 - oxidoreductase activity
Cellular Component: GO:0005739 - mitochondrion

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


Subunit of: pyruvate dehydrogenase E1 component (testis)

Species: Homo sapiens

Subunit composition of pyruvate dehydrogenase E1 component (testis) = [PDHB]2[PDHA2]2
         pyruvate dehydrogenase E1 component β subunit = PDHB (summary available)
         Pyruvate dehydrogenase E1 component subunit alpha, testis-specific form, mitochondrial = PDHA2

Credits:
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 E1 component (somatic)

Species: Homo sapiens

Subunit composition of pyruvate dehydrogenase E1 component (somatic) = [PDHB]2[PDHA1]2
         pyruvate dehydrogenase E1 component β subunit = PDHB (summary available)
         pyruvate dehydrogenase E1 component α subunit (somatic) = PDHA1 (summary available)

Component of: pyruvate dehydrogenase complex (extended summary available)

Summary:
The α2β2-heterotetrameric human pyruvate dehydrogenase, one of the three main components of the pyruvate dehydrogenase complex, utilizes the thiamin pyrophosphate cofactor to cleave the Cα-C(=O) bond of pyruvate, followed by reductive acetyl transfer to lipoyl-dihydrolipoamide acetyltransferase (the E2 component of the pyruvate dehydrogenase complex).

The crystal structure of the holo-form of the E1 enzyme was resolved at 1.95-A resolution [Ciszak03].

Credits:
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: 1.2.4.1

pyruvate + a [pyruvate dehydrogenase E2 protein] N6-lipoyl-L-lysine + H+ <=> a [pyruvate dehydrogenase E2 protein] N6-S-acetyldihydrolipoyl-L-lysine + CO2

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

Credits:
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

Summary:
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].

Credits:
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

Exons/Introns:


References

Brown04: Brown RM, Head RA, Boubriak II, Leonard JV, Thomas NH, Brown GK (2004). "Mutations in the gene for the E1beta subunit: a novel cause of pyruvate dehydrogenase deficiency." Hum Genet 115(2);123-7. PMID: 15138885

Chun90: Chun K, Mackay N, Willard HF, Robinson BH (1990). "Isolation, characterization and chromosomal localization of cDNA clones for the E1 beta subunit of the pyruvate dehydrogenase complex." Eur J Biochem 194(2);587-92. PMID: 1702713

Ciszak03: Ciszak EM, Korotchkina LG, Dominiak PM, Sidhu S, Patel MS (2003). "Structural basis for flip-flop action of thiamin pyrophosphate-dependent enzymes revealed by human pyruvate dehydrogenase." J Biol Chem 278(23);21240-6. PMID: 12651851

Ho88: Ho L, Javed AA, Pepin RA, Thekkumkara TJ, Raefsky C, Mole JE, Caliendo AM, Kwon MS, Kerr DS, Patel MS (1988). "Identification of a cDNA clone for the beta-subunit of the pyruvate dehydrogenase component of human pyruvate dehydrogenase complex." Biochem Biophys Res Commun 150(3);904-8. PMID: 2829898

Ho90: Ho L, Patel MS (1990). "Cloning and cDNA sequence of the beta-subunit component of human pyruvate dehydrogenase complex." Gene 86(2);297-302. PMID: 2323578

Huh90: Huh TL, Casazza JP, Huh JW, Chi YT, Song BJ (1990). "Characterization of two cDNA clones for pyruvate dehydrogenase E1 beta subunit and its regulation in tricarboxylic acid cycle-deficient fibroblast." J Biol Chem 265(22);13320-6. PMID: 2376596

Koike88: Koike K, Ohta S, Urata Y, Kagawa Y, Koike M (1988). "Cloning and sequencing of cDNAs encoding alpha and beta subunits of human pyruvate dehydrogenase." Proc Natl Acad Sci U S A 85(1);41-5. PMID: 3422424

Koike90: Koike K, Urata Y, Koike M (1990). "Molecular cloning and characterization of human pyruvate dehydrogenase beta subunit gene." Proc Natl Acad Sci U S A 87(15);5594-7. PMID: 2377599

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

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


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 SRI International Pathway Tools version 18.5 on Sun Dec 21, 2014, BIOCYC13B.