Pyruvate dehydrogenase Pyruvate Dehydrogenase (PDH) and the TCA Cycle (Krebs cycle)


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Proteins > Pyruvate dehydrogenase (PDH)

Pyruvate dehydrogenase (PDH)

Alternate Names:pyruvate dehydrogenase complex, PDC
Structure and Function:The pyruvate dehydrogenase complex (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.

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 physically to become substrate for the next in a reaction sequence that is a prototype substrate channeling mechanism. In addition, one structural subunit has been identified, the E3 binding protein. This protein supports 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-1alpha, 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.

Disease Associations:PDH deficiencies, diabetes, starvation, sepsis, and possibly Alzheimer’s have been linked to altered PDH functioning.
Monoclonal Antibodies
Cat. No.NameReactivityApps.Amount
MSP01c PDH Capture Antibody Human, BovineIP100 �g
MSP03 PDH subunit E1 alpha Antibody Human, Bovine, Rat and MouseWB, ICC, ICE, FLOW100 �g
MSP07 PDH subunit E1 alpha Antibody Human, Bovine, Mouse, Rat, Drosophila, C. elegansWB, ICC, FLOW100 �g
MSP04 PDH subunit E1 beta Antibody Human, Bovine, Mouse, RatWB100 �g
MSP05 PDH subunit E2 Antibody Human, BovineWB, ICC, IHC, ICE, FLOW100 �g
MSP06 PDH subunit E2/E3bp Antibody Human, Bovine, Rat, MouseWB, ICC, IHC, FLOW100 �g
MSP49 PDK1 Antibody Human, Bovine, Rat, MouseWB, ICC, ICE100 �g
MSP52 PDK4 antibody HumanWB100 �g
MSP56 Pan-PDK Antibody HumanWB100 �g
ab133982 PDP2 antibodyHumanWB100 �g
Antibody Cocktails
Cat. No.NameReactivityAmount
MSP02 PDH WB Antibody Cocktail Human, Bovine150 �g
300 �g
In-Cell ELISA Kits
Cat. No.NameReactivityAmount
MSP47 PhosphoPDH In-Cell ELISA Kit (IR) Human, Rat, Mouse, Bovine2 x 96 Tests
MSP48 PhosphoPDH In-Cell ELISA Kit (Colorimetric) Human, Rat, Mouse, Bovine2 x 96 Tests
ab125299 Hif1 alpha+ PDK1 Hypoxia Human In Cell ELISA Kit (IR) Human96 Tests
Protein Quantity Assays
Cat. No.NameReactivityAmount
MS964 PDH E1 alpha protein (PDHA1) ELISA Kit (ab115342) Human, Bovine, Mouse, Rat96 Tests
MS965 Phospho S232 PDH E1 alpha protein (PDHA1) ELISA Kit (ab115343) Human, Bovine, Mouse, Rat96 Tests
MS966 Phospho S293 PDH E1 alpha protein (PDHA1) ELISA Kit (ab115344) Human, Bovine, Mouse, Rat96 Tests
MS967 Phospho S300 PDH E1 alpha protein (PDHA1) ELISA Kit (ab115345) Human, Bovine, Mouse, Rat96 Tests
ab126582 Pyruvate Dehydrogenase Kinase 4 (PDK4) Human ELISA Kit Human96 Tests
MSP19 PDH Protein Quantity Microplate Assay Kit Human, Bovine, Mouse, Rat96 Tests
MSP20 PDH Combo (Activity + Quantity) Microplate Assay Kit Human, Bovine, Mouse, Rat96 Tests
MSP31 PDH Protein Quantity
Dipstick Assay Kit
Human, Bovine, Mouse, Rat30 Tests
90 tests
ab181415 PDH E1 alpha protein (PDHA1) Human ELISA Kit Human96 Tests
Enzyme Activity Assays
Cat. No.NameReactivityAmount
MSP18 PDH Enzyme Activity Microplate Assay Kit Human, Bovine, Mouse, Rat96 Tests
MSP20 PDH Combo (Activity + Quantity) Microplate Assay Kit Human, Bovine, Mouse, Rat96 Tests
MSP30 PDH Enzyme Activity
Dipstick Assay Kit
Human, Bovine, Mouse, Rat, Porcine30 Tests
90 tests
Multiplexing Arrays
Cat. No.NameReactivityAmount
MSX31 MetaPath™ MitoDisease
4-Plex Dipstick Array
Human30 Tests
90 tests
Immunocapture Kits
Cat. No.NameReactivityAmount
MSP01 PDH Immunocapture Kit Human, Bovine250 �g
500 �g
750 �g
ab133988 PDH Immunocapture Kit (rodent) Rat, mouse100 �g
Recombinant Proteins
Cat. No.NameSourceAmount
MSP41 PDH Kinase 1 (PDK1) Human50 �g
MSP42 PDH Kinase 2 (PDK2) Human50 �g
MSP43 PDH Kinase 3 (PDK3) Human50 �g
MSP44 PDH Kinase 4 (PDK4) Human50 �g
MSP45 PDH Phosphatase 1 (PDP1) Human50 �g
MSP46 PDH Phosphatase 2 (PDP2) Human50 �g

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Related Pathways:

Intermediary Metabolism Overview

Acetyl-CoA Metabolism: Key Nodes

Glycolysis

Krebs Cycle

Pyruvate Metabolism: Key Nodes

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