Pyruvate dehydrogenase (PDH)

The key regulatory site in cellular metabolism

PDH Application guide

View our optimal range to measure all aspects of the pyruvate dehydrogenase complex (PDH). PDH deficiencies, diabetes, starvation, sepsis, and possibly Alzheimer's disease have been linked to altered PDH functioning.

  1. Structure and function
  2. Related products
  3. PDH Phosphorylation/Dephosphorylation protocols & references

1. Structure and function

PDH is at the centre of aerobic carbohydrate metabolism. It is localized in the matrix space of mitochondria where it catalyzes the irreversible oxidative decarboxylation of pyruvate entering the organelle to produce acetyl-CoA, NADH and CO2. Thus it links and regulates the flow of energy in cells by determining when pyruvate should be used for oxidative phosphorylation versus "neutralized" to lactic acid to allow continued glycolysis. At the same time the control of acetyl Co-A directly influences fatty acid oxidation and production of ketone bodies.

Pyruvate dehydrogenase pathway

Figure 1. Five sequential reactions of PDH-catalyzed oxidative decarboxylation of pyruvate to Acetyl Coenzyme A.

 

PDH is a large complex (MW around 9 MDa) consisting of multiple copies of three enzymes: pyruvate dehydrogenase (E1), dihydrolipoamide transacetylase (E2) and dihydrolipoamide dehydrogenase (E3). The E1 enzyme is a tetramer comprised of two alpha and two beta subunits and is present in 30 copies. In the mammalian enzyme, 60 copies of E2 forms the core with the other subunits organized regularly around its periphery. Intermediates of one enzyme are passed to become substrate for the next in a reaction sequence that is a prototype substrate channeling mechanism. In addition, one structural subunit, the E3 binding protein, has been identified to protein support the interactions between the E2 and E3 subunits.

The activity of PDH is regulated by reversible phosphorylation of three serine residues on the E1alpha subunit. The phosphorylation of these sites is catalyzed by PDH kinases (PDK). There are four known isoforms of PDKs that are distributed differently in tissues. Their expressions are regulated differently by factors such as starvation, hypoxia and utilization of glucose and fatty acids in various tissues. In addition, transcription regulators such as PGC-1 alpha, retinoic acid and the glucocorticoid receptor are involved.

Dephosporylation to restore the activity of PDH is catalyzed by PDH phosphatases (PDP). There are two known isoforms of PDPs, which are expressed differently in various tissues; PDP1 is present in high levels in skeletal muscle and PDP2 in liver and adipocytes.

PDH pathway

Figure 2. A schematic of the reactions controlling pyruvate dehydrogenase.

Each of the PDK’s and PDP’s is under transcriptional control in response to different cellular stress events.

2. Related products

Mouse monoclonal antibodies

NameReacts withApplicationsMitoSciences codeAbcam code
Pyruvate Dehydrogenase Immunocapture antibody [15D3G9C11] Hu, Cow IP MSP01c ab109866
Pyruvate Dehydrogenase E1-alpha subunit antibody [9H9AF5] Hu, Ms, Rat, Cow Flow Cyt, ICC/IF, In-Cell ELISA, WB MSP03 ab110330
Pyruvate Dehydrogenase E1-alpha subunit antibody [8D10E6] Hu, Ms, Rat, Ce, Cow, Dm IP MSP07 ab110334
Pyruvate Dehydrogenase E1 beta subunit antibody [17A5E2H8] Hu, Ms, Rat, Cow WB MSP04 ab110331
Pyruvate Dehydrogenase E2 antibody [15D3G9C11] Hu, Cow Flow Cyt, ICC/IF, IHC-P, In-Cell ELISA, WB MSP05 ab110332
Pyruvate dehydrogenase E2/E3bp antibody [13G2AE2BH5] Hu, Ms, Rat, Cow Flow Cyt, ICC/IF, IHC-P, WB MSP06 ab110333
Mitochondrial Pyruvate dehydrogenase kinase 1 antibody [2H3AA11] Hu, Cow Flow Cyt, ICC/IF, In-Cell ELISA, WB MSP49 ab110335
PDK4 antibody [1C2BG5] Hu WB MSP52 ab110336
Pan PDK antibody [3H5BE12] Hu WB MSP56 ab115321

Antibody cocktails

NameReacts withApplicationsMitoSciences codeAbcam code
MitoProfile® Pyruvate dehydrogenase (PDH) WB Antibody Cocktail Hu, Cow WB MSP02 ab110416

In-Cell ELISA kits

NameReacts withAmountsMitoSciences codeAbcam code
PhosphoPDH In-Cell ELISA Kit (IR) Hu, Ms, Rat, Cow 2 x 96 tests MSP47 ab110218
PhosphoPDH In-Cell ELISA Kit (Colorimetric) Hu, Ms, Rat, Cow 2 x 96 tests MSP48 ab110219
Hif1 + PDK1 Hypoxia Human In Cell ELISA Kit Hu 1 x 96 tests MS1008 ab125299

Protein quantity assays

NameReacts withAmountsMitoSciences codeAbcam code
Pyruvate dehydrogenase (PDH) Protein Quantity Microplate Assay Kit Hu, Ms, Rat, Cow 1 x 96 tests MSP19 ab110174
Pyruvate dehydrogenase (PDH) Combo (Activity + Quantity) Microplate Assay Kit Hu, Ms, Rat, Cow 1 x 96 tests MSP20 ab110671
Pyruvate dehydrogenase (PDH) Protein Quantity Dipstick Assay Kit Hu, Ms, Rat, Cow 1 x 90 tests MSP31 ab109883

Enzyme activity assays

NameReacts withAmountsMitoSciences codeAbcam code
Pyruvate dehydrogenase (PDH) Enzyme Activity Microplate Assay Kit Hu, Ms, Rat, Cow 1 x 96 tests MSP18 ab109902
Pyruvate dehydrogenase (PDH) Combo (Activity + Quantity) Microplate Assay Kit Hu, Ms, Rat, Cow 1 x 96 tests MSP20 ab110671
Pyruvate dehydrogenase (PDH) Enzyme Activity Dipstick Assay Kit Hu, Ms, Rat, Cow, Pig 1 x 90 tests MSP30 ab109882

ELISA Kits

NameReacts withAmountsMitoSciences codeAbcam code
PDH E1 alpha protein (PDHA1) ELISA Kit Hu, Ms, Rat, Cow 1 x 96 tests MS964 ab115342
Phospho S232 PDH E1 alpha protein (PDHA1) ELISA Kit Hu, Ms, Rat, Cow 1 x 96 tests MS965 ab115343
Phospho S293 PDH E1 alpha protein (PDHA1) ELISA Kit Hu, Ms, Rat, Cow 1 x 96 tests MS966 ab115344
Phospho S300 PDH E1 alpha protein (PDHA1) ELISA Kit Hu, Ms, Rat, Cow 4 x 96 tests MS967 ab115345

Multiplex arrays

NameReacts withAmountsMitoSciences codeAbcam code
MetaPath™ Mito Disease 4-Plex Dipstick Array Hu 1 x 90 tests MSX31 ab109879

Immunocapture kits

NameReacts withAmountsMitoSciences codeAbcam code
PDH Immunocapture Kit Hu, Cow 250 µg MSP01 ab109802

Recombinant proteins

PDH Kinases (PDKs) deactivate PDH by reversible phosphorylation. In humans and rodents, 4 PDK's are present in an organ-dependent manner. In all cases, PDK's are physically part of the PDH complex (binding via lipoyl domain 2 of E2), and they phosphorylate the E1 subunit at 3 specific serine residues. PDH phosphatases remove the phosphorylation and restore activity of PDH.

NameSpeciesApplicationsMitoSciences codeAbcam code
Mitochondrial Pyruvate dehydrogenase kinase 1 protein Hu sELISA, FuncS MSP41 ab110359
PDK2 protein Hu sELISA, FuncS MSP42 ab110354
PDK3 protein Hu sELISA, FuncS MSP43 ab110355
PDK4 protein Hu sELISA, FuncS MSP44 ab110356
PDP1 protein Hu sELISA, FuncS MSP45 ab110357
PDP2 protein Hu sELISA, FuncS MSP46 ab110358

3. PDH Phosphorylation/Dephosphorylation protocols & references

Download the following PDH protocols.

References on the Structure, Function and Regulation of PDH.

  • Sugden MC, Bulmer K, & Holness MJ. (2001) “Fuel Sensing Mechanisms Integrating Lipid and Carbohydrate Utilization.” Biochem Soc Trans. 29, 272-278. PMID 11356166
  • Patel MS & Korotchkina LG. (2006) “Regulation of the Pyruvate Dehydrogenase Complex.” Biochem Soc Trans. 34, 217-222. PMID 16545080
  • Utilization.” Biochem Soc Trans. 29, 272-278. PMID 11356166
  • Roche TE & Hiromasa Y. (2007) “Pyruvate dehydrogenase kinase regulatory mechanisms and inhibition in diabetes, heart disease and cancer.” Cell Mol Life. 64, 830-849. PMID 17310282
  • Degenhardt T, et al. (2007) “Three members of the human pyruvate dehydrogenase kinase gene family are direct targets of peroxisome proliferator - activator receptor ß/delta. JJ Mol Biol. 372, 341-355. PMID 17669420

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