Pyruvate dehydrogenase kinase
Encyclopedia
Pyruvate dehydrogenase kinase (also pyruvate dehydrogenase complex kinase, PDC kinase, or PDK; ) is a kinase
enzyme
which acts to inactivate the enzyme pyruvate dehydrogenase
by phosphorylating it using ATP
.
PDK thus participates in the regulation of the pyruvate dehydrogenase complex of which pyruvate dehydrogenase is the first component. Both PDK and the pyruvate dehydrogenase complex are located in the mitochondrial matrix
of eukaryote
s. The complex acts to convert pyruvate (a product of glycolysis
in the cytosol
) to acetyl-coA
, which is then oxidized in the mitochondria to produce energy, in the citric acid cycle
. By downregulating the activity of this complex, PDK will decrease the oxidation of pyruvate in mitochondria and increase the conversion of pyruvate to lactate
in the cytosol.
The opposite action of PDK, namely the dephosphorylation and activation of pyruvate dehydrogenase, is catalyzed by a phosphoprotein phosphatase
called pyruvate dehydrogenase phosphatase
.
(Pyruvate dehydrogenase kinase should not be confused with Phosphoinositide-dependent kinase-1
, which is also sometimes known as "PDK1".)
, NADH and acetyl-CoA
.
It is inhibited by ADP
, NAD+, CoA-SH and pyruvate.
Pyruvate dehydrogenase kinase is also inhibited by the drug dichloroacetate which has been tried as a treatment of certain metabolic diseases and is under investigation as a treatment of cancer.
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
enzyme
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...
which acts to inactivate the enzyme 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...
by phosphorylating it using ATP
Adenosine 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...
.
PDK thus participates in the regulation of the pyruvate dehydrogenase complex of which pyruvate dehydrogenase is the first component. Both PDK and the pyruvate dehydrogenase complex are 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 eukaryote
Eukaryote
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...
s. The complex acts to convert pyruvate (a product of glycolysis
Glycolysis
Glycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
in 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....
) to 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 then oxidized in the mitochondria to produce energy, 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...
. By downregulating the activity of this complex, PDK will decrease the oxidation of pyruvate in mitochondria and increase the conversion of pyruvate to lactate
Lactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...
in the cytosol.
The opposite action of PDK, namely the dephosphorylation and activation of pyruvate dehydrogenase, is catalyzed by a phosphoprotein phosphatase
Phosphoprotein phosphatase
Phosphoprotein phosphatase is an enzyme that dephosphorylates certain phosphorylated proteins.In some contexts, "Phosphoprotein phosphatase" is equated with serine/threonine specific protein phosphatase, and classified under ....
called 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...
.
(Pyruvate dehydrogenase kinase should not be confused with Phosphoinositide-dependent kinase-1
Phosphoinositide-dependent kinase-1
In the field of biochemistry, 3-phosphoinositide dependent protein kinase-1, also known as PDPK1 is a protein which in humans is encoded by the PDPK1 gene.PDPK1 is also known as "PDK1"...
, which is also sometimes known as "PDK1".)
Regulation
Pyruvate dehydrogenase kinase is stimulated by 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...
, NADH 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...
.
It is inhibited by 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....
, NAD+, CoA-SH and pyruvate.
Pyruvate dehydrogenase kinase is also inhibited by the drug dichloroacetate which has been tried as a treatment of certain metabolic diseases and is under investigation as a treatment of cancer.