Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

1.2.4.1

Official Name

pyruvate dehydrogenase (acetyl-transferring)

Name from literature

pyruvate dehydrogenase

Pathway from literature

acetyl coenzyme A synthesis/synthesis of acetylcholine

Pathway from KEGG

Amino Acid Metabolism; Valine, leucine and isoleucine biosynthesis; map00290

Carbohydrate Metabolism; Pyruvate metabolism; map00620

Carbohydrate Metabolism; Glycolysis / Gluconeogenesis; map00010

Amino Acid Metabolism; Alanine and aspartate metabolism; map00252

Carbohydrate Metabolism; Butanoate metabolism; map00650

Organisms

Human (9606)

Genome localization

Xp22.2-p22.1[5160 ], 3p21.1-p14.2[5162 ], 4q22-q23[5161 ],

Comments

Contains thiamine diphosphate. It is a component (in multiple copies) of the multienzyme pyruvate dehydrogenase complex in which it is bound to a core of molecules of EC 2.3.1.12, dihydrolipoyllysine-residue acetyltransferase, which also binds multiple copies of EC 1.8.1.4, dihydrolipoyl dehydrogenase. It does not act on free lipoamide or lipoyllysine, but only on the lipoyllysine residue in EC 2.3.1.12.

Rate-limiting Description

"This uptake rate corresponds to a TCA cycle rate of 4-5 mmol min-1 kg-1, which is of the same magnitude as the activity of oxyglutarate dehydrogenase and pyruvate dehydrogenase, suggesting that these enzymes may be rate limiting for oxygen uptake when an isolated muscle is exercising." (10759582)

Regulatory Information

Regulatory type

Detail

phosphorylation;

"Short-term elevation in plasma non-esterified fatty acids at rest increases PDH-E1alpha phosphorylation, but exercise overrules this effect and phosphorylation leads to even dephosphorylation during exercise with intralipid infusion." (17065338)

phosphorylation;

P08559

phosphorylation;

P11177

phosphorylation;

P29803

phosphorylation;

P08559:from_uniprot:232_Phosphoserine

phosphorylation;

P08559:from_uniprot:289_Phosphotyrosine

phosphorylation;

P08559:from_uniprot:293_Phosphoserine

phosphorylation;

P08559:from_uniprot:295_Phosphoserine

phosphorylation;

P08559:from_uniprot:300_Phosphoserine

phosphorylation;

P08559:from_uniprot:301_Phosphotyrosine

phosphorylation;

P11177:from_uniprot:67_Phosphotyrosine

phosphorylation;

P29803:from_uniprot:230_Phosphoserine

phosphorylation;

P29803:from_uniprot:291_Phosphoserine

phosphorylation;

P29803:from_uniprot:298_Phosphoserine

transcriptional level;

"Computer-aided transcription factor binding consensus sequence analysis revealed the presence of PPAR, HOXD, MyoD and other tissue-specific transcription factor binding sites. Promoter function analysis using the chloramphenicol acetyltransferase reporter gene indicated that the -2.2 kb/-1.7 kb and -5.9 kb/-5.2 kb regions of the E1alpha promoter may possess negative regulatory elements which are likely to function in a tissue-specific manner." (10350629)

transcriptional factor;

"The DNase I protected regions contained consensus nucleotide sequences recognized by GATA-1, Sp1, IgNF-A, Lva, bicoid Q9, NF-kB, HNF-5, H4TF-1, WAP5, and ADH transription factors. Transient expression of chloramphenicol acetyltransferase (CAT) suggested the possible presence of negative elements located within the sequence from -2316 to -930, whereas deletion constructs containing -929 to +32 and -98 to +32 DNA sequences showed approximately 7- and 20-fold increases in CAT activity over the basal CAT activity. Additional studies indicated the presence of an orientation-dependent cis element (or elements) within the region from -282 to -397 that acts as an enhancer or a repressor upon a heterologous thymidine kinase promoter." (7827076)

Gene ontology

Gene ontology

GO:0006099 (P) tricarboxylic acid cycle [P11177 ];
GO:0005759 (C) mitochondrial matrix [P29803, P08559, P11177 ];
GO:0006096 (P) glycolysis [P29803, P08559, P11177 ];
GO:0004739 (F) pyruvate dehydrogenase (acetyl-transferring... [P29803, P08559, A5YPB6, P11177 ];
GO:0005515 (F) protein binding [P08559 ];
GO:0055114 (P) oxidation reduction [P29803, P08559, A5YPB6, P11177 ];

Tissue expression

Tissue From HPRD

Kidney [02420 ];
Heart [01530, 02420 ];
Skin fibroblast [01530, 02420 ];
Testis [01531 ];
Skin [02420 ];
Liver [01530, 02420 ];
Skeletal muscle [02420 ];
Brain [02420 ];

Tissue specificity

Testis. Expressed in postmeiotic spermatogenic cells [P29803 ];

Ubiquitous [P08559 ];

Subcellular localization

Localization

mitochondrion [P29803, P08559, P11177 ];

Disease relevance

Disease

Defects in PDHB are a cause of pyruvate dehydrogenase E1 component deficiency (PDHE1 deficiency) [MIM:312170]. PDHE1 deficiency is the most common enzyme defect in patients with primary lactic acidosis. It is associated with variable clinical phenotypes ranging from neonatal death to prolonged survival complicated by developmental delay, seizures, ataxia, apnea, and in some cases to an X-linked form of Leigh syndrome (LS) (Leigh encephalomyelopathy) [P11177 ];

Defects in PDHA1 are a cause of pyruvate decarboxylase E1 component deficiency (PDHE1 deficiency) [MIM:312170]. PDHE1 deficiency is the most common enzyme defect in patients with primary lactic acidosis. It is associated with variable clinical phenotypes ranging from neonatal death to prolonged survival complicated by developmental delay, seizures, ataxia, apnea, and in some cases to an X-linked form of Leigh syndrome (LS) (Leigh encephalomyelopathy) [P08559 ];

Defects in PDHA1 are the cause of X-linked Leigh syndrome (LS) [MIM:308930]. LS is an early-onset progressive neurodegenerative disorder with a characteristic neuropathology consisting of focal, bilateral lesions in one or more areas of the central nervous system, including the brainstem, thalamus, basal ganglia, cerebellum, and spinal cord. The lesions are areas of demyelination, gliosis, necrosis, spongiosis, or capillary proliferation. Clinical symptoms depend on which areas of the central nervous system are involved. The most common underlying cause is a defect in oxidative phosphorylation. LS may be a feature of a deficiency of any of the mitochondrial respiratory chain complexes [P08559 ];

Links

SwissProt

A5YPB6; P08559; P11177; P29803

Entrez Gene

5160; 5161; 5162

HPRD

02420; 01531; 01530



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  Last Modified: 2009-03-24  
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