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Pyruvate dehydrogenase complex (PDC) is a complex of three enzymes that converts pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. [1] 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 .
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 ...
Pyruvate oxidation is the step that connects glycolysis and the Krebs cycle. [4] In glycolysis, a single glucose molecule (6 carbons) is split into 2 pyruvates (3 carbons each). Because of this, the link reaction occurs twice for each glucose molecule to produce a total of 2 acetyl-CoA molecules, which can then enter the Krebs cycle.
Following glycolysis, the citric acid cycle is activated by the production of acetyl-CoA. The oxidation of pyruvate by pyruvate dehydrogenase in the matrix produces CO 2, acetyl-CoA, and NADH. Beta oxidation of fatty acids serves as an alternate catabolic pathway that produces acetyl-CoA, NADH, and FADH 2. [1]
Glycolysis is the metabolic pathway that converts glucose (C 6 H 12 O 6) into pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). [ 1 ]
In eukaryotes, glycolysis occurs in the cytoplasm, pyruvate decarboxylation in the mitochondria, the citric acid cycle within the mitochondrial matrix, and oxidative phosphorylation via the electron transport chain on the mitochondrial cristae. Thus pyruvate dehydrogenase complexes (containing the dihydrolipoyl transacetylase enzymes) are found ...
Pyruvate decarboxylase occurs as a dimer of dimers with two active sites shared between the monomers of each dimer. The enzyme contains a beta-alpha-beta structure, yielding parallel beta-sheets. It contains 563 residue subunits in each dimer; the enzyme has strong intermonomer attractions, but the dimers loosely interact to form a loose tetramer.
Pyruvate decarboxylation is the step that connects glycolysis and the Krebs cycle and is regulated by the pyruvate dehydrogenase complex when blood glucose levels are high. [9] Otherwise, fatty acid β-oxidation occurs, and acetyl-CoA is required to generate ATP through the Krebs cycle. [ 10 ]