Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that transform pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and this complex links the glycolysis metabolic pathway to the citric acid cycle. Pyruvate decarboxylation is also known as the "pyruvate dehydrogenase reaction" because it also involves the oxidation of pyruvate. Image File history File links Merge-arrows. ... It has been suggested that this article or section be merged with pyruvate dehydrogenase complex. ... Ribbon diagram of the enzyme TIM, surrounded by the space-filling model of the protein. ... Pyruvate (CH3COCOO−) is the ionized form of pyruvic acid. ... Categories: Biochemistry stubs | Thiols ... It has been suggested that this article or section be merged with pyruvate dehydrogenase complex. ... Overview of the citric acid cycle The citric acid cycle (also known as the tricarboxylic acid cycle, the TCA cycle, or the Krebs cycle, after Hans Adolf Krebs who identified the cycle) is a series of chemical reactions of central importance in all living cells that use oxygen as part... Cellular respiration describes the metabolism reactions and processes that take place in a cell to obtain biochemical energy from fuel molecules. ... Glycolysis is a metabolic pathway by which a 6-carbon glucose (Glc) molecule is oxidized to two molecules of pyruvic acid (Pyr). ... In biochemistry, a metabolic pathway is a series of chemical reactions occurring within a cell. ...

This multi-enzyme complex is related structurally and functionally to the oxoglutarate dehydrogenase and branched-chain oxo-acid dehydrogenase multi-enzyme complexes. Oxoglutarate dehydrogenase (aka α-ketoglutarate dehydrogenase) is an enzyme most commonly known for its role in the citric acid cycle. ... The Branched-chain alpha-keto acid dehydrogenase complex is a combination of enzymes responsible for the degradation of the branched chain amino acids. ...

Reaction

The reaction catalysed by pyruvate dehydrogenase complex is:

Pyruvate (CH3COCOO−) is the ionized form of pyruvic acid. ... Acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. ... Image File history File links Pyruvate_wpmp. ... Image File history File links Acetyl_co-A_wpmp. ... Coenzyme A (CoA, CoASH, or HSCoA) is a coenzyme, notable for its role in the synthesis and oxidization of fatty acids, and the oxidation of pyruvate in the citric acid cycle. ... Image File history File links Biochem_reaction_arrow_foward_YYNN_horiz_med. ...

Structure & function in eukaryotes

Pyruvate dehydrogenase complex is located in the mitochondrial matrix of eukaryotes. It consists of a total of 60 subunits, organized into three functional proteins: In biology, the word matrix is used for the material between animal or plant cells, or generally the material (or tissue) in which more specialized structures are embedded, and also specifically for one part of the mitochondrion. ... Kingdoms Eukaryotes are organisms with complex cells, in which the genetic material is organized into membrane-bound nuclei. ... In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles (or coassembles) with other protein molecules to form a multimeric or oligomeric protein. ...

A cofactor is the following: In mathematics a cofactor is the minor of an element of a square matrix. ... Pyruvate dehydrogenase is an enzyme (E1) in the pyruvate dehydrogenase complex (PDC). ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... For the similarly spelled nucleic acid, see Thymine Thiamine or thiamin, also known as vitamin B1, is one of the B vitamins. ... Dihydrolipoyl transacetylase (or dihydrolipoamide acetyltransferase) is the structural and catalytic core of the pyruvate dehydrogenase multienzyme complex, playing a crucial role in the architecture of the complex. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... Lipoic acid, also known as α-lipoic acid (alpha lipoic acid) or thioctic acid, has formula C8H14S2O2 and systematic name 5-(1,2-dithiolan-3-yl)pentanoic acid. ... Coenzyme A (CoA, CoASH, or HSCoA) is a coenzyme, notable for its role in the synthesis and oxidization of fatty acids, and the oxidation of pyruvate in the citric acid cycle. ... Dihydrolipoamide dehydrogenase is a flavoprotein enzyme which degrades lipoamide, and produces dihydrolipoamide. ... The Enzyme Commission number (EC number) is a numerical classification scheme for enzymes, based on the chemical reactions they catalyze. ... For other uses, see FAD (disambiguation). ... Nicotinamide adenine dinucleotide (NAD+ or in older notation DPN+) is an important coenzyme found in cells. ...

Pyruvate dehydrogenase (E1)

Initially, pyruvate and thiamine pyrophosphate (TPP) are bound by pyruvate dehydrogenase subunits. The thiazolium ring of TPP is in a zwitterionic form, and the anionic C2 carbon performs a nucleophilic attack on the C2 (ketone) carbonyl of pyruvate. The resulting hemithioacetal undergoes Decarboxylation to produce an acyl anion equivalent (see cyanohydrin or aldehyde-dithiane umpolung chemistry, as well as benzoin condensation). This anion attacks S1 of an oxidized lipoate species that is attached to a lysine residue. In a ring-opening S_N2-like mechanism, S2 is displaced as a sulfide or sulfhydryl moiety. Subsequent collapse of the tetrahedral hemithioacetal ejects thiazole, releasing the TPP cofactor and generating a thioacetate on S1 of lipoate. The E1-catalyzed process is the rate-limiting one of the whole pyruvate dehydrogenase complex. Pyruvate (CH3COCOO−) is the ionized form of pyruvic acid. ... For the similarly spelled nucleic acid, see Thymine Thiamine or thiamin, also known as vitamin B1, is one of the B vitamins. ... Pyruvate dehydrogenase is an enzyme (E1) in the pyruvate dehydrogenase complex (PDC). ... Thiazole, or 1,3-thiazole, is a clear to pale yellow flammable liquid and pyridine-like odor with the molecular formula C3H3NS. It is a 5-membered ring, in which two of the vertices of the ring are nitrogen and sulfur, and the other three are carbons [1]. Thiazole is... A zwitterion (from German Zwitter — hybrid, hermaphrodite) is a compound with acidic and basic groups in the same molecule. ... An anion is an ion with negative charge. ... A Decarboxylation is any chemical reaction in which a carboxyl group (-COOH) is split off from a compound as carbon dioxide (CO2). ... Cyanohydrin is any of several compounds that contain both the CN and OH radicals. ... Umpolung or polarity inversion in organic chemistry is the chemical modification of a functional group with the aim the reversal of polarity of that group. ... The Benzoin condensation is a condensation reaction between two aromatic aldehydes, especially benzaldehyde that is catalyzed by a cyanide. ... Lysine is one of the 20 amino acids normally found in proteins. ...

Dihydrolipoyl transacetylase (E2)

At this point, the lipoate-thioester functionality is translocated into the dihydrolipoyl transacetylase (E2) active site, where a transacylation reaction transfers the acetyl from the "swinging arm" of lipoyl to the thiol of coenzyme A. This produces Acetyl-CoA, which is released from the enzyme complex and subsequently enters the citric acid cycle. Dihydrolipoyl transacetylase (or dihydrolipoamide acetyltransferase) is the structural and catalytic core of the pyruvate dehydrogenase multienzyme complex, playing a crucial role in the architecture of the complex. ... Coenzyme A (CoA, CoASH, or HSCoA) is a coenzyme, notable for its role in the synthesis and oxidization of fatty acids, and the oxidation of pyruvate in the citric acid cycle. ... Categories: Biochemistry stubs | Thiols ... Overview of the citric acid cycle The citric acid cycle (also known as the tricarboxylic acid cycle, the TCA cycle, or the Krebs cycle, after Hans Adolf Krebs who identified the cycle) is a series of chemical reactions of central importance in all living cells that use oxygen as part...

Dihydrolipoyl dehydrogenase (E3)

The dihydrolipoate, still bound to a lysine residue of the complex, then migrates to the dihydrolipoyl dehydrogenase (E3) active site where it undergoes a flavin-mediated oxidation, identical in chemistry to disulfide isomerase. First, FAD oxidizes dihydrolipoate back to its lipoate resting state, producing FADH₂. Then, a [[nicotinamide adenine dinucleotide|NAD⁺ cofactor oxidizes FADH₂ back to its FAD resting state, producing NADH. Lipoic acid, also known as α-lipoic acid (alpha lipoic acid) or thioctic acid, has formula C8H14S2O2 and systematic name 5-(1,2-dithiolan-3-yl)pentanoic acid. ... Dihydrolipoamide dehydrogenase is a flavoprotein enzyme which degrades lipoamide, and produces dihydrolipoamide. ... Riboflavin Flavin is a vaginal ring whose biochemical smell is pungent. ... For other uses, see FAD (disambiguation). ... A cofactor is the following: In mathematics a cofactor is the minor of an element of a square matrix. ...

Regulation

Pyruvate dehydrogenase is inhibited when one or more of the three following ratios are increased: ATP/ADP, NADH/NAD⁺ and acetyl-CoA/CoA. Adenosine 5-triphosphate (ATP) is a multifunctional nucleotide that is most important as a molecular currency of intracellular energy transfer. ... Adenosine diphosphate, abbreviated ADP, is a nucleotide. ... Nicotinamide adenine dinucleotide (NAD+) Nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) are two important coenzymes found in cells. ... Categories: Biochemistry stubs | Thiols ... Coenzyme A (CoA, CoASH, or HSCoA) is a coenzyme, notable for its role in the synthesis and oxidization of fatty acids, and the oxidation of pyruvate in the citric acid cycle. ...

In eukaryotes PDC is tightly regulated by its own specific pyruvate dehydrogenase kinase (PDK) and pyruvate dehydrogenase phosphatase (PDP). Pyruvate dehydrogenase kinase is a kinase enzyme which acts to phosphorylate Pyruvate dehydrogenase. ... Pyruvate dehydrogenase phosphatase (PDP) is an enzyme which serves to reverse the effects of pyruvate dehydrogenase kinase upon pyruvate dehydrogenase. ...

• PDK phosphorylates three specific serine residues on E1 with different affinities. Phosphorylation of any one of them renders E1 (and in consequence the entire complex) inactive.
• Dephosphorylation of E1 by PDP reinstates complex activity.

Products of the reaction act as allosteric inhibitors of the PDH complex, but they also act on PDH kinase, activating it. Substrates in turn inhibit the PDH complex.

During starvation, PDK increases in amount in most tissues, including skeletal muscle, via increased gene transcription. Under the same conditions, the amount of PDP decreases. The resulting inhibition of PDC prevents muscle and other tissues from catabolizing glucose and gluconeogenesis precursors. Metabolism shifts toward fat utilization, while muscle protein breakdown to supply gluconeogenesis precursors is minimized, and available glucose is spared for use by the brain.

Calcium ion has a role in regulation of PDH complex in muscle tissue, because it activates PDH phosphatase, stimulating glycolysis on its release into the cytosol - during muscle contraction. General Name, Symbol, Number calcium, Ca, 20 Chemical series alkaline earth metals Group, Period, Block 2, 4, s Appearance silvery white Standard atomic weight 40. ... Glycolysis is a metabolic pathway by which a 6-carbon glucose (Glc) molecule is oxidized to two molecules of pyruvic acid (Pyr). ... A top-down view of skeletal muscle A muscle contraction (also known as a muscle twitch or simply twitch) occurs when a muscle cell (called a muscle fiber) lengthens or shortens. ...

Structural differerences between species

PDC is a large complex composed of multiple copies of 3 or 4 subunits depending on species.

Gram-negative bacteria

In Gram-negative bacteria, e.g. Escherichia coli, PDC consists of a central octahedral core made up from 24 molecules of dihydrolipoyl transacetylase (E2). Bacteria that are Gram-negative are not stained dark blue or violet by Gram staining, in contrast to Gram-positive bacteria. ... E. coli redirects here. ... Dihydrolipoyl transacetylase (or dihydrolipoamide acetyltransferase) is the structural and catalytic core of the pyruvate dehydrogenase multienzyme complex, playing a crucial role in the architecture of the complex. ...

Up to 24 copies of pyruvate decarboxylase (E1) and 12 molecules of dihydrolipoyl dehydrogenase (E3) bind to the outside of the E2 core. Pyruvate decarboxylase is a homotetrameric enzyme(EC 4. ... Dihydrolipoamide dehydrogenase is a flavoprotein enzyme which degrades lipoamide, and produces dihydrolipoamide. ...

Gram-positive bacteria and eukaryotes

In contrast, in Gram-positive bacteria (e.g. Bacillus stearothermophilus) and eukaryotes the central PDC core contains 60 E2 molecules arranged into an icosahedron. Gram-positive bacteria are those that are stained dark blue or violet by gram staining, in contrast to gram-negative bacteria, which are not affected by the stain. ... Bacillus stearothermophilus is a rod-shaped, Gram-positive bacteria and a member of the division Firmicutes. ...

Eukaryotes also contain 12 copies of an additional core protein, E3 binding protein (E3BP). The exact location of E3BP is not completely clear. Cryo-electron microscopy has established that E3BP binds to each of the icosahedral faces in yeast. However, it has been suggested that it replaces an equivalent number of E2 molecules in the bovine PDC core. E3 binding protein is a component of the pyruvate dehydrogenase complex found only in eukaryotes. ...

Up to 60 E1 or E3 molecules can associate with the E2 core from Gram-positive bacteria - binding is mutually exclusive. In eukaryotes E2 is specifically bound by E2, while E3 associates with E3BP. It is thought that up to 30 E1 and 6 E3 enzymes are present, although the exact number of molecules can vary in vivo and often reflects the metabolic requirements of the tissue in question.

See also

• Pyruvate dehydrogenase deficiency

Pyruvate Dehydrogenase Deficiency (PDHA) is a human genetic disease. ...

Related links

• http://www.dentistry.leeds.ac.uk/biochem/MBWeb/mb1/part2/krebs.htm#animat1 - animation of the general mechanism of the PDH complex (link on upper right) at University of Leeds
• MeSH Pyruvate+Dehydrogenase+Complex