Pyruvate dehydrogenase
Encyclopedia
Pyruvate dehydrogenase complex (PDC) is a complex of three enzyme
s 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.
This multi-enzyme complex is related structurally and functionally to the oxoglutarate dehydrogenase
and branched-chain oxo-acid dehydrogenase multi-enzyme
complexes.
in three functional proteins. Pyruvate dehydrogenase complex is located in the mitochondrial matrix
of eukaryotes. It is organized in dodecahedral symmetry, and consists of a total of 96 subunits
, organized into three functional proteins in the human enzyme:
(TPP or vitamin B1
) are bound by Pyruvate dehydrogenase
subunits. The thiazolium
ring of TPP is in a zwitterion
ic 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 SN2-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 step of the whole pyruvate dehydrogenase complex.
(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
. E2 can also be known as lipoamide reductase-transacetylase.
, 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 NAD+
cofactor
oxidizes FADH2 back to its FAD resting state, producing NADH.
/ADP
, NADH/NAD+ and acetyl-CoA
/CoA
.
In eukaryotes PDC is tightly regulated by its own specific pyruvate dehydrogenase kinase
(PDK) and pyruvate dehydrogenase phosphatase
(PDP), deactivating and activating it respectively.
Products of the reaction act as allosteric inhibitors of the PDC, because they activate PDK. Substrates in turn inhibit PDK, and thus, reactivating PDC.
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 PDC in muscle tissue, because it activates PDP, stimulating glycolysis
on its release into the cytosol - during muscle contraction
.
cells the Swanson conversion occurs inside the mitochondria, after transport of the substrate, pyruvate, from the cytosol
. The transport of pyruvate into the mitochondria is via a transport protein
and is active
, consuming energy
. Passive diffusion of pyruvate into the mitochondria is impossible because it carries a negative charge.
On entry to the mitochondria the pyruvate decarboxylation occurs, producing acetyl CoA. This irreversible reaction traps the acetyl CoA within the mitochondria (the acetyl-CoA can only be transported out of the mitochondrial matrix under conditions of high oxaloacetate via the citrate shuttle, a TCA intermediate that is normally sparse). The carbon dioxide produced by this reaction is nonpolar and small, and can diffuse out of the mitochondria and out of the cell.
In prokaryote
s, which have no mitochondria, this reaction is either carried out in the cytosol, or not at all.
bacteria, e.g. Escherichia coli
, PDC consists of a central cubic core made up from 24 molecules of dihydrolipoyl transacetylase
(E2).
Up to 24 copies of Pyruvate dehydrogenase
(E1) and 12 molecules of dihydrolipoyl dehydrogenase (E3) bind to the outside of the E2 core.
bacteria (e.g. Bacillus stearothermophilus
) and eukaryotes the central PDC core contains 60 E2 molecules arranged into an icosahedron.
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.
Up to 60 E1 or E3 molecules can associate with the E2 core from Gram-positive bacteria - binding is mutually exclusive. In eukaryotes E1 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.
pyruvate dehydrogenase complex, human full-length and truncated E2 (tE2) cores of PDC, expressed in E. coli
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
s that transform pyruvate into acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...
by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
to carry out cellular respiration
Cellular respiration
Cellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...
, and this complex links the glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
metabolic pathway
Metabolic pathway
In biochemistry, metabolic pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by a series of chemical reactions. Enzymes catalyze these reactions, and often require dietary minerals, vitamins, and other cofactors in order to function...
to the citric acid cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
. Pyruvate decarboxylation is also known as the "pyruvate dehydrogenase reaction" because it also involves the oxidation of pyruvate.
This multi-enzyme complex is related structurally and functionally to the oxoglutarate dehydrogenase
Oxoglutarate dehydrogenase
The oxoglutarate dehydrogenase complex or α-ketoglutarate dehydrogenase complex is an enzyme complex, most commonly known for its role in the citric acid cycle.-Units:...
and branched-chain oxo-acid dehydrogenase multi-enzyme
Branched-chain alpha-keto acid dehydrogenase complex
The branched-chain α-keto acid dehydrogenase complex is a combination of enzymes responsible for the degradation of the branched-chain amino acids...
complexes.
Reaction
The reaction catalysed by pyruvate dehydrogenase complex is:Structure & function in eukaryotes
Pyruvate dehydrogenase complex is organized in cubic symmetry in prokaryotes, having 60 subunitsProtein subunit
In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...
in three functional proteins. Pyruvate dehydrogenase complex is located in the mitochondrial matrix
Mitochondrial matrix
In the mitochondrion, the matrix contains soluble enzymes that catalyze the oxidation of pyruvate and other small organic molecules.The mitochondrial matrix also contains the mitochondria's DNA and ribosomes. The word "matrix" stems from the fact that this space is viscous, compared to the...
of eukaryotes. It is organized in dodecahedral symmetry, and consists of a total of 96 subunits
Protein subunit
In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...
, organized into three functional proteins in the human enzyme:
| Enzyme | Abbrev. | Cofactor Cofactor (biochemistry) A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations.... (s) | # subunits prokaryotes | # subunits eukaryotes |
|---|---|---|---|---|
| pyruvate dehydrogenase Pyruvate dehydrogenase Pyruvate dehydrogenase complex 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... |
E1 | TPP (thiamine pyrophosphate) | 24 | 30 |
| dihydrolipoyl transacetylase Dihydrolipoyl transacetylase Dihydrolipoyl transacetylase is an enzyme component of the multienzyme pyruvate dehydrogenase complex. The pyruvate dehydrogenase complex is responsible for the pyruvate decarboxylation step that links glycolysis to the citric acid cycle... |
E2 | lipoate Lipoic acid Lipoic acid , also known as α-lipoic acid and Alpha Lipoic Acid is an organosulfur compound derived from octanoic acid. LA contains two vicinal sulfur atoms attached via a disulfide bond and is thus considered to be oxidized... coenzyme A Coenzyme A Coenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate... |
24 | 60 |
| dihydrolipoyl dehydrogenase |
E3 | FAD FAD In biochemistry, flavin adenine dinucleotide is a redox cofactor involved in several important reactions in metabolism. FAD can exist in two different redox states, which it converts between by accepting or donating electrons. The molecule consists of a riboflavin moiety bound to the phosphate... NAD Nicotinamide adenine dinucleotide Nicotinamide adenine dinucleotide, abbreviated NAD, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide.In metabolism, NAD is involved... + |
12 | 12 |
Pyruvate decarboxylase(E1)
Initially, pyruvate and thiamine pyrophosphateThiamine
Thiamine or thiamin or vitamin B1 , named as the "thio-vitamine" is a water-soluble vitamin of the B complex. First named aneurin for the detrimental neurological effects if not present in the diet, it was eventually assigned the generic descriptor name vitamin B1. Its phosphate derivatives are...
(TPP or vitamin B1
Thiamine
Thiamine or thiamin or vitamin B1 , named as the "thio-vitamine" is a water-soluble vitamin of the B complex. First named aneurin for the detrimental neurological effects if not present in the diet, it was eventually assigned the generic descriptor name vitamin B1. Its phosphate derivatives are...
) are bound by Pyruvate dehydrogenase
Pyruvate dehydrogenase
Pyruvate dehydrogenase complex 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...
subunits. The thiazolium
Thiazole
Thiazole, or 1,3-thiazole, is a heterocyclic compound that contains both sulfur and nitrogen; the term 'thiazole' also refers to a large family of derivatives. Thiazole itself is a pale yellow liquid with a pyridine-like odor and the molecular formula C3H3NS...
ring of TPP is in a zwitterion
Zwitterion
In chemistry, a zwitterion is a neutral molecule with a positive and a negative electrical charge at different locations within that molecule. Zwitterions are sometimes also called inner salts.-Examples:...
ic form, and the anionic C2 carbon performs a nucleophilic attack on the C2 (ketone) carbonyl of pyruvate. The resulting hemithioacetal undergoes decarboxylation
Decarboxylation
Decarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...
to produce an acyl anion equivalent (see cyanohydrin
Cyanohydrin
A cyanohydrin is a functional group found in organic compounds. Cyanohydrins have the formula R2CCN, where R is H, alkyl, or aryl. Cyanohydrins are industrially important precursors to carboxylic acids and some amino acids...
or aldehyde-dithiane umpolung
Umpolung
Umpolung or polarity inversion in organic chemistry is the chemical modification of a functional group with the aim of the reversal of polarity of that group. This modification allows secondary reactions of this functional group that would otherwise not be possible. The concept was introduced by...
chemistry, as well as benzoin condensation
Benzoin condensation
The benzoin condensation is a reaction between two aromatic aldehydes, particularly benzaldehyde. The reaction is catalyzed by a nucleophile such as the cyanide anion or an N-heterocyclic carbene. The reaction product is an aromatic acyloin with benzoin as the parent compound...
). This anion attacks S1 of an oxidized lipoate species that is attached to a lysine
Lysine
Lysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
residue. In a ring-opening SN2-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 step of the whole pyruvate dehydrogenase complex.
Dihydrolipoyl transacetylase (E2)
At this point, the lipoate-thioester functionality is translocated into the dihydrolipoyl transacetylaseDihydrolipoyl transacetylase
Dihydrolipoyl transacetylase is an enzyme component of the multienzyme pyruvate dehydrogenase complex. The pyruvate dehydrogenase complex is responsible for the pyruvate decarboxylation step that links glycolysis to the citric acid cycle...
(E2) active site, where a transacylation reaction transfers the acetyl from the "swinging arm" of lipoyl to the thiol of coenzyme A
Coenzyme A
Coenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...
. This produces acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...
, which is released from the enzyme complex and subsequently enters the citric acid cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
. E2 can also be known as lipoamide reductase-transacetylase.
Dihydrolipoyl dehydrogenase (E3)
The dihydrolipoateLipoic acid
Lipoic acid , also known as α-lipoic acid and Alpha Lipoic Acid is an organosulfur compound derived from octanoic acid. LA contains two vicinal sulfur atoms attached via a disulfide bond and is thus considered to be oxidized...
, 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
FAD
In biochemistry, flavin adenine dinucleotide is a redox cofactor involved in several important reactions in metabolism. FAD can exist in two different redox states, which it converts between by accepting or donating electrons. The molecule consists of a riboflavin moiety bound to the phosphate...
oxidizes dihydrolipoate back to its lipoate resting state, producing FADH2. Then, a NAD+
Nicotinamide adenine dinucleotide
Nicotinamide adenine dinucleotide, abbreviated NAD, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide.In metabolism, NAD is involved...
cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
oxidizes FADH2 back to its FAD resting state, producing NADH.
Regulation
Pyruvate dehydrogenase is inhibited when one or more of the three following ratios are increased: ATPAdenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
/ADP
Adenosine diphosphate
Adenosine diphosphate, abbreviated ADP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside adenosine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine....
, NADH/NAD+ and acetyl-CoA
Acetyl-CoA
Acetyl coenzyme A or acetyl-CoA is an important molecule in metabolism, used in many biochemical reactions. Its main function is to convey the carbon atoms within the acetyl group to the citric acid cycle to be oxidized for energy production. In chemical structure, acetyl-CoA is the thioester...
/CoA
Coenzyme A
Coenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...
.
In eukaryotes PDC is tightly regulated by its own specific pyruvate dehydrogenase kinase
Pyruvate dehydrogenase kinase
Pyruvate dehydrogenase kinase is a kinase enzyme which acts to inactivate the enzyme pyruvate dehydrogenase by phosphorylating it using ATP....
(PDK) and pyruvate dehydrogenase phosphatase
Pyruvate dehydrogenase phosphatase
pyruvate dehyrogenase phosphatase catalytic subunit 1 , also known as protein phosphatase 2C, is an enzyme that in humans is encoded by the PDP1gene...
(PDP), deactivating and activating it respectively.
- 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 PDC, because they activate PDK. Substrates in turn inhibit PDK, and thus, reactivating PDC.
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
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
ion has a role in regulation of PDC in muscle tissue, because it activates PDP, stimulating glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
on its release into the cytosol - during muscle contraction
Muscle contraction
Muscle fiber generates tension through the action of actin and myosin cross-bridge cycling. While under tension, the muscle may lengthen, shorten, or remain the same...
.
Localization of pyruvate decarboxylation
In eukaryoticEukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
cells the Swanson conversion occurs inside the mitochondria, after transport of the substrate, pyruvate, from the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
. The transport of pyruvate into the mitochondria is via a transport protein
Transport protein
A membrane transport protein is a membrane protein involved in the movement of ions, small molecules, or macromolecules, such as another protein across a biological membrane. Transport proteins are integral membrane proteins; that is they exist within and span the membrane across which they...
and is active
Active transport
Active transport is the movement of a substance against its concentration gradient . In all cells, this is usually concerned with accumulating high concentrations of molecules that the cell needs, such as ions, glucose, and amino acids. If the process uses chemical energy, such as from adenosine...
, consuming energy
Energy
In physics, energy is an indirectly observed quantity. It is often understood as the ability a physical system has to do work on other physical systems...
. Passive diffusion of pyruvate into the mitochondria is impossible because it carries a negative charge.
On entry to the mitochondria the pyruvate decarboxylation occurs, producing acetyl CoA. This irreversible reaction traps the acetyl CoA within the mitochondria (the acetyl-CoA can only be transported out of the mitochondrial matrix under conditions of high oxaloacetate via the citrate shuttle, a TCA intermediate that is normally sparse). The carbon dioxide produced by this reaction is nonpolar and small, and can diffuse out of the mitochondria and out of the cell.
In prokaryote
Prokaryote
The prokaryotes are a group of organisms that lack a cell nucleus , or any other membrane-bound organelles. The organisms that have a cell nucleus are called eukaryotes. Most prokaryotes are unicellular, but a few such as myxobacteria have multicellular stages in their life cycles...
s, which have no mitochondria, this reaction is either carried out in the cytosol, or not at all.
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-negativeGram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
bacteria, e.g. Escherichia coli
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...
, PDC consists of a central cubic core made up from 24 molecules of dihydrolipoyl transacetylase
Dihydrolipoyl transacetylase
Dihydrolipoyl transacetylase is an enzyme component of the multienzyme pyruvate dehydrogenase complex. The pyruvate dehydrogenase complex is responsible for the pyruvate decarboxylation step that links glycolysis to the citric acid cycle...
(E2).
Up to 24 copies of Pyruvate dehydrogenase
Pyruvate dehydrogenase
Pyruvate dehydrogenase complex 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...
(E1) and 12 molecules of dihydrolipoyl dehydrogenase (E3) bind to the outside of the E2 core.
Gram-positive bacteria and eukaryotes
In contrast, in Gram-positiveGram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...
bacteria (e.g. Bacillus stearothermophilus
Bacillus stearothermophilus
Bacillus stearothermophilus is a rod-shaped, Gram-positive bacterium and a member of the division Firmicutes. The bacteria is a thermophile and is widely distributed in soil, hot springs, ocean sediment, and is a cause of spoilage in food products. It will grow within a temperature range of 30-75...
) and eukaryotes the central PDC core contains 60 E2 molecules arranged into an icosahedron.
Eukaryotes also contain 12 copies of an additional core protein, E3 binding protein
E3 binding protein
E3 binding protein also known as pyruvate dehydrogenase protein X component, mitochondrial is a protein that in humans is encoded by the PDHX gene...
(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.
Up to 60 E1 or E3 molecules can associate with the E2 core from Gram-positive bacteria - binding is mutually exclusive. In eukaryotes E1 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.
Related links
- http://www.dentistry.leeds.ac.uk/biochem/MBWeb/mb1/part2/krebs.htm#animat1 - animation of the general mechanism of the PDC (link on upper right) at University of LeedsUniversity of LeedsThe University of Leeds is a British Redbrick university located in the city of Leeds, West Yorkshire, England...
3D structures
, bovine kidneyKidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
pyruvate dehydrogenase complex, human full-length and truncated E2 (tE2) cores of PDC, expressed in E. coli