RGD Reference Report - Regulation of mammalian pyruvate dehydrogenase complex by phosphorylation: complexity of multiple phosphorylation sites and kinases. - Rat Genome Database

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Regulation of mammalian pyruvate dehydrogenase complex by phosphorylation: complexity of multiple phosphorylation sites and kinases.

Authors: Patel, MS  Korotchkina, LG 
Citation: Patel MS and Korotchkina LG, Exp Mol Med. 2001 Dec 31;33(4):191-7.
RGD ID: 2307427
Pubmed: PMID:11795479   (View Abstract at PubMed)
DOI: DOI:10.1038/emm.2001.32   (Journal Full-text)

This review summarizes the recent developments on the regulation of human pyruvate dehydrogenase complex (PDC) by site-specific phosphorylation by four kinases. Mutagenic analysis of the three phosphorylation sites of human pyruvate dehydrogenase (E1) showed the site-independent mechanism of phosphorylation as well as site-independent dephosphorylation of the three phosphorylation sites and the importance of each phosphorylation site for the inactivation of E1. Both the negative charge and size of the group introduced at site 1 were involved in human E1 inactivation. Mechanism of inactivation of E1 was suggested to be site-specific. Phosphorylation of site 1 affected E1 interaction with the lipoyl domain of dihydrolipoamide acetyltransferase, whereas phosphorylation site 3 appeared to be closer to the thiamine pyrophosphate (TPP)-binding region affecting coenzyme interaction with human E1. Four isoenzymes of pyruvate dehydrogenase kinase (PDK) showed different specificity for the three phosphorylation sites of E1. All four PDKs phosphorylated sites 1 and 2 in PDC with different rates, and only PDK1 phosphorylated site 3. PDK2 was maximally stimulated by the reduction/acetylation of the lipoyl groups of E2. Presence of the multiple phosphorylation sites and isoenzymes of PDK is important for the tissue-specific regulation of PDC under different physiological conditions.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DLATHumanpyruvate metabolic pathway   TAS  RGD 
DLDHumanpyruvate metabolic pathway   TAS  RGD 
DlatRatpyruvate metabolic pathway   ISODLAT (Homo sapiens) RGD 
DlatMousepyruvate metabolic pathway   ISODLAT (Homo sapiens) RGD 
DldRatpyruvate metabolic pathway   ISO RGD 
DldMousepyruvate metabolic pathway   ISO RGD 
PDHA1Humanpyruvate metabolic pathway   TAS  RGD 
PDHA2Humanpyruvate metabolic pathway   TAS  RGD 
PDHBHumanpyruvate metabolic pathway   TAS  RGD 
PDHXHumanpyruvate metabolic pathway   TAS  RGD 
PDK1Humanpyruvate metabolic pathway   TAS  RGD 
PDK2Humanpyruvate metabolic pathway   TAS  RGD 
PDK3Humanpyruvate metabolic pathway   TAS  RGD 
PDK4Humanpyruvate metabolic pathway   TAS  RGD 
Pdha1Ratpyruvate metabolic pathway   ISOPDHA1 (Homo sapiens) RGD 
Pdha1Mousepyruvate metabolic pathway   ISOPDHA1 (Homo sapiens) RGD 
Pdha2Ratpyruvate metabolic pathway   ISOPDHA2 (Homo sapiens) RGD 
Pdha2Mousepyruvate metabolic pathway   ISOPDHA2 (Homo sapiens) RGD 
PdhbRatpyruvate metabolic pathway   ISOPDHB (Homo sapiens) RGD 
PdhbMousepyruvate metabolic pathway   ISOPDHB (Homo sapiens) RGD 
PdhxRatpyruvate metabolic pathway   ISOAbl2_mapped (Rattus norvegicus) RGD 
PdhxMousepyruvate metabolic pathway   ISOAbl2_mapped (Rattus norvegicus) RGD 
Pdk1Ratpyruvate metabolic pathway   ISOPDK1 (Homo sapiens) RGD 
Pdk1Mousepyruvate metabolic pathway   ISOPDK1 (Homo sapiens) RGD 
Pdk2Ratpyruvate metabolic pathway   ISOPDK2 (Homo sapiens) RGD 
Pdk2Mousepyruvate metabolic pathway   ISOPDK2 (Homo sapiens) RGD 
Pdk3Mousepyruvate metabolic pathway   ISOPDK3 (Homo sapiens) RGD 
Pdk3Ratpyruvate metabolic pathway   ISOPDK3 (Homo sapiens) RGD 
Pdk4Ratpyruvate metabolic pathway   ISOPDK4 (Homo sapiens) RGD 
Pdk4Mousepyruvate metabolic pathway   ISOPDK4 (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Dlat  (dihydrolipoamide S-acetyltransferase)
Dld  (dihydrolipoamide dehydrogenase)
Pdha1  (pyruvate dehydrogenase E1 subunit alpha 1)
Pdha2  (pyruvate dehydrogenase E1 subunit alpha 2)
Pdhb  (pyruvate dehydrogenase E1 subunit beta)
Pdhx  (pyruvate dehydrogenase complex, component X)
Pdk1  (pyruvate dehydrogenase kinase 1)
Pdk2  (pyruvate dehydrogenase kinase 2)
Pdk3  (pyruvate dehydrogenase kinase 3)
Pdk4  (pyruvate dehydrogenase kinase 4)

Genes (Mus musculus)
Dlat  (dihydrolipoamide S-acetyltransferase)
Dld  (dihydrolipoamide dehydrogenase)
Pdha1  (pyruvate dehydrogenase E1 alpha 1)
Pdha2  (pyruvate dehydrogenase E1 alpha 2)
Pdhb  (pyruvate dehydrogenase (lipoamide) beta)
Pdhx  (pyruvate dehydrogenase complex, component X)
Pdk1  (pyruvate dehydrogenase kinase, isoenzyme 1)
Pdk2  (pyruvate dehydrogenase kinase, isoenzyme 2)
Pdk3  (pyruvate dehydrogenase kinase, isoenzyme 3)
Pdk4  (pyruvate dehydrogenase kinase, isoenzyme 4)

Genes (Homo sapiens)
DLAT  (dihydrolipoamide S-acetyltransferase)
DLD  (dihydrolipoamide dehydrogenase)
PDHA1  (pyruvate dehydrogenase E1 subunit alpha 1)
PDHA2  (pyruvate dehydrogenase E1 subunit alpha 2)
PDHB  (pyruvate dehydrogenase E1 subunit beta)
PDHX  (pyruvate dehydrogenase complex component X)
PDK1  (pyruvate dehydrogenase kinase 1)
PDK2  (pyruvate dehydrogenase kinase 2)
PDK3  (pyruvate dehydrogenase kinase 3)
PDK4  (pyruvate dehydrogenase kinase 4)


Additional Information