Pathways

Pyruvate, or its conjugate acid pyruvic acid, is important in many metabolic pathways. It can be created from glucose via glycolysis, it can be converted to carbohydrates or fatty acids, and can be used in fermentation as well. It is an energy supply in either the citric acid cycle or fermentation, depending on the oxygen present for the cells. In this pathway, pyruvic acid can be obtained from sources such as tyrosine metabolism. Pyruvic acid can then react with thiamine pyrophosphate, using pyruvate dehyderogenase as an enzyme, removing a carbon dioxide and forming 2-(a-hydroxyethyl)thiamine diphosphate. This then reacts with a protein N6-(lipoyl)lysine compound, again using pyruvate dehydrogenase as the enzyme, reforming thiamine pyrophosphate as well as S-acetyldihydrolipoamide-E. This then can be converted to and from acetyl-CoA by the addition of CoA with a dihydrolipoic transacetylase, which also forms protein N6-(dihydrolipoyl)lysine. This can also be converted to and from protein N6-(lipoyl)lysine by dihydrolipoyl dehydrogenase. Acetyl-CoA can interact with acetyl-CoA thiol esterase to add a water molecule and remove the CoA, forming acetic acid. Acetic acid can also be formed from acetylphosphate, which interacts with acylphosphatase to add a water molecule and remove the phosphate group. From here, acetic acid can interact with acetyl-CoA synthetase to form acetyl adenylate reversibly. Acetyl adenylate can also be formed directly from acetyl-CoA via the same acetyl-CoA synthetase enzyme. Acetyl-CoA can also interact with acetyl-CoA carboxylase to form malonyl-CoA, a compound which, along with acetyl-CoA, is used in fatty acid biosynthesis and elongation. Alternately, acetyl-CoA can interact with acetoacetyl-CoA thiolase, which takes two molecules of acetyl-CoA and combines them, removing one CoA and forming acetoacetyl-CoA in the mitochondria. Another pathway pyruvic acid can go through is its conversion to oxalacetic acid. Oxalacetic acid can then be converted to and from L-malic acid by malate dehydrogenase which adds a hydrogen ion to the oxalacetic acid. L-malic acid can then either interact with NAD-specific malic enzyme to be converted to and from pyruvic acid, or fumarate hydratase, converting it to and from fumaric acid, both of which occur in the mitochondria. Oxalacetic acid can also be converted to and from phosphoenolpyruvic acid by phosphoenolpyruvate carboxylase. This can then interact with pyruvate kinase, removing its phosphate group and adding it to ADP, forming both ATP and pyruvic acid. Pyruvic acid can also be formed in a pathway that starts with D-lactaldehyde. D-lactaldehyde can be converted to and from pyruvaldehyde by NADPH-glyoxylate reductase, which removes a hydrogen ion, forming a second carbonyl in the molecule. pyruvaldehyde can then be further converted to and from S-lactoylglutathione by lactoylglutathione lyase, which adds a glutathione to the pyruvaldehyde. Following this, S-lactoylglutathione enters the mitochondria and interacts with a hydroxyacylglutathione hydrolase which adds a water molecule and removes the glutathione, which is important in maintaining mitochondrial redox homeostasis. The D-lactic acid produced then can react with ferricytochrome c to form ferrocytochrome c and pyruvic acid, catalyzed by a lactic acid dehydrogenase, also in the mitochondria.

Pyruvate is an intermediate compound in the metabolism of fats, proteins, and carbohydrates. It can be formed from glucose via glycolysis or the transamination of alanine. It can be converted into Acetyl-CoA to be used as the primary energy source for the TCA cycle, or converted into oxaloacetate to replenish TCA cycle intermediates. Pyruvate can also be used to synthesize carbohydrates, fatty acids, ketone bodies, alanine, and steroids. In conditions of inssuficient oxygen or in cells with few mitochondria, pyruvate is reduced to lactate in order to re-oxidize NADH back into NAD+ Pyruvate participates in several key reactions and pathways. In glycolysis, phosphoenolpyruvate (PEP) is converted to pyruvate by pyruvate kinase in an highly exergonic and irreversible reaction. In gluconeogenesis, pyruvate carboxylase and PEP carboxykinase are needed to catalyze the conversion of pyruvate to PEP. In fatty acid synthesis, the pyruvate dehydrogenase complex decarboxylates pyruvate to produce acetyl-CoA. In gluconeogenesis, the carboxylation by pyruvate carboxylase produces oxaloacetate. The fate of pyruvate depends on the cell energy charge. In cells or tissues with a high energy charge pyruvate is directed toward gluconeogenesis, but when the energy charge is low pyruvate is preferentially oxidized to CO2 and H2O in the TCA cycle, with generation of 15 equivalents of ATP per pyruvate. The enzymatic activities of the TCA cycle are located in the mitochondrion. When transported into the mitochondrion, pyruvate encounters two principal metabolizing enzymes: pyruvate carboxylase (a gluconeogenic enzyme) and pyruvate dehydrogenase (PDH). With a high cell-energy charge, acetyl-CoA, is able allosterically to activate pyruvate carboxylase, directing pyruvate toward gluconeogenesis. When the energy charge is low CoA is not acylated, pyruvate carboxylase is inactive, and pyruvate is preferentially metabolized via the PDH complex and the enzymes of the TCA cycle to CO2 and H2O.

Pyruvate is an intermediate compound in the metabolism of fats, proteins, and carbohydrates. It can be formed from glucose via glycolysis or the transamination of alanine. It can be converted into Acetyl-CoA to be used as the primary energy source for the TCA cycle, or converted into oxaloacetate to replenish TCA cycle intermediates. Pyruvate can also be used to synthesize carbohydrates, fatty acids, ketone bodies, alanine, and steroids. In conditions of inssuficient oxygen or in cells with few mitochondria, pyruvate is reduced to lactate in order to re-oxidize NADH back into NAD+ Pyruvate participates in several key reactions and pathways. In glycolysis, phosphoenolpyruvate (PEP) is converted to pyruvate by pyruvate kinase in an highly exergonic and irreversible reaction. In gluconeogenesis, pyruvate carboxylase and PEP carboxykinase are needed to catalyze the conversion of pyruvate to PEP. In fatty acid synthesis, the pyruvate dehydrogenase complex decarboxylates pyruvate to produce acetyl-CoA. In gluconeogenesis, the carboxylation by pyruvate carboxylase produces oxaloacetate. The fate of pyruvate depends on the cell energy charge. In cells or tissues with a high energy charge pyruvate is directed toward gluconeogenesis, but when the energy charge is low pyruvate is preferentially oxidized to CO2 and H2O in the TCA cycle, with generation of 15 equivalents of ATP per pyruvate. The enzymatic activities of the TCA cycle are located in the mitochondrion. When transported into the mitochondrion, pyruvate encounters two principal metabolizing enzymes: pyruvate carboxylase (a gluconeogenic enzyme) and pyruvate dehydrogenase (PDH). With a high cell-energy charge, acetyl-CoA, is able allosterically to activate pyruvate carboxylase, directing pyruvate toward gluconeogenesis. When the energy charge is low CoA is not acylated, pyruvate carboxylase is inactive, and pyruvate is preferentially metabolized via the PDH complex and the enzymes of the TCA cycle to CO2 and H2O.

The metabolism of pyruvate begins with its biosynthesis which can happen through 5 different sets of reactions. A) Lactaldehyde reacts with an NADPH dependent methylglyoxal reductase results in the release of a pyruvaldehyde. Pyruvaldehyde reacts with glutathione through a lactylglutathione lyase resulting in the release of s-lactoylglutathione. The latter compound then reacts with water through a hydroxyacylglutathione hydrolase resulting in the release of glutathione and D-lactic acid. Lactic acid then reacts with a ferricytochrome c through a D-lactate dehydrogenase resulting in the release of ferrocytochrome c, a hydrogen ion and pyruvic acid. B) L-lactic acid reacts with a ferricytochrome c through a L-lactate dehydrogenase resulting in the release of ferrocytochrome c, a hydrogen ion and pyruvic acid. C)Phosphoenolpyruvic acid reacts with an ADP through pyruvate kinase II resulting in the release of pyruvic acid. D)Phosphoenolpyruvic acid reacts in a reversible reaction with an ADP or ATP driven phosphoenolpyruvate carboxykinase resulting in the release of oxalacetic acid which reacts with ADP driven pyruvate carboxylase resulting in the release of pyruvic acid. E)L-malic acid reacts in a reversible reaction through NAD driven malate dehydrogenase resulting in the release of pyruvic acid. Pyruvic acid is degraded through 2 sets of reactions a)Pyruvic acid reacts with a pyruvate decarboxylase resulting in the release of acetaldehyde. This compound then reacts with alcohol dehydrogenase resulting in the release of ethanol b)Pyruvic acid reacts with a Pyruvate dehydrogenase complex resulting in the release of 2-(a-Hydroxyethyl)thiamine diphosphate. The latter compound reacts with a Pyruvate dehydrogenase complex resulting in the release of S-Acetyldihydrolipoamide-E reacts with a Pyruvate dehydrogenase complex resulting in the release of acetyl-CoA. Acetyl CoA can then be metabolized through different reactions to produce the resulting acetate, acetyl adenylate, isopropylmalic acid acetoacetyl coa, malonyl coa or homocitric acid

Pyruvate is an intermediate compound in the metabolism of fats, proteins, and carbohydrates. It can be formed from glucose via glycolysis or the transamination of alanine. It can be converted into Acetyl-CoA to be used as the primary energy source for the TCA cycle, or converted into oxaloacetate to replenish TCA cycle intermediates. Pyruvate can also be used to synthesize carbohydrates, fatty acids, ketone bodies, alanine, and steroids. In conditions of inssuficient oxygen or in cells with few mitochondria, pyruvate is reduced to lactate in order to re-oxidize NADH back into NAD+ Pyruvate participates in several key reactions and pathways. In glycolysis, phosphoenolpyruvate (PEP) is converted to pyruvate by pyruvate kinase in an highly exergonic and irreversible reaction. In gluconeogenesis, pyruvate carboxylase and PEP carboxykinase are needed to catalyze the conversion of pyruvate to PEP. In fatty acid synthesis, the pyruvate dehydrogenase complex decarboxylates pyruvate to produce acetyl-CoA. In gluconeogenesis, the carboxylation by pyruvate carboxylase produces oxaloacetate. The fate of pyruvate depends on the cell energy charge. In cells or tissues with a high energy charge pyruvate is directed toward gluconeogenesis, but when the energy charge is low pyruvate is preferentially oxidized to CO2 and H2O in the TCA cycle, with generation of 15 equivalents of ATP per pyruvate. The enzymatic activities of the TCA cycle are located in the mitochondrion. When transported into the mitochondrion, pyruvate encounters two principal metabolizing enzymes: pyruvate carboxylase (a gluconeogenic enzyme) and pyruvate dehydrogenase (PDH). With a high cell-energy charge, acetyl-CoA, is able allosterically to activate pyruvate carboxylase, directing pyruvate toward gluconeogenesis. When the energy charge is low CoA is not acylated, pyruvate carboxylase is inactive, and pyruvate is preferentially metabolized via the PDH complex and the enzymes of the TCA cycle to CO2 and H2O.

Pyruvate is an intermediate compound in the metabolism of fats, proteins, and carbohydrates. It can be formed from glucose via glycolysis or the transamination of alanine. It can be converted into Acetyl-CoA to be used as the primary energy source for the TCA cycle, or converted into oxaloacetate to replenish TCA cycle intermediates. Pyruvate can also be used to synthesize carbohydrates, fatty acids, ketone bodies, alanine, and steroids. In conditions of inssuficient oxygen or in cells with few mitochondria, pyruvate is reduced to lactate in order to re-oxidize NADH back into NAD+ Pyruvate participates in several key reactions and pathways. In glycolysis, phosphoenolpyruvate (PEP) is converted to pyruvate by pyruvate kinase in an highly exergonic and irreversible reaction. In gluconeogenesis, pyruvate carboxylase and PEP carboxykinase are needed to catalyze the conversion of pyruvate to PEP. In fatty acid synthesis, the pyruvate dehydrogenase complex decarboxylates pyruvate to produce acetyl-CoA. In gluconeogenesis, the carboxylation by pyruvate carboxylase produces oxaloacetate. The fate of pyruvate depends on the cell energy charge. In cells or tissues with a high energy charge pyruvate is directed toward gluconeogenesis, but when the energy charge is low pyruvate is preferentially oxidized to CO2 and H2O in the TCA cycle, with generation of 15 equivalents of ATP per pyruvate. The enzymatic activities of the TCA cycle are located in the mitochondrion. When transported into the mitochondrion, pyruvate encounters two principal metabolizing enzymes: pyruvate carboxylase (a gluconeogenic enzyme) and pyruvate dehydrogenase (PDH). With a high cell-energy charge, acetyl-CoA, is able allosterically to activate pyruvate carboxylase, directing pyruvate toward gluconeogenesis. When the energy charge is low CoA is not acylated, pyruvate carboxylase is inactive, and pyruvate is preferentially metabolized via the PDH complex and the enzymes of the TCA cycle to CO2 and H2O.

Pyruvate is an intermediate compound in the metabolism of fats, proteins, and carbohydrates. It can be formed from glucose via glycolysis or the transamination of alanine. It can be converted into Acetyl-CoA to be used as the primary energy source for the TCA cycle, or converted into oxaloacetate to replenish TCA cycle intermediates. Pyruvate can also be used to synthesize carbohydrates, fatty acids, ketone bodies, alanine, and steroids. In conditions of inssuficient oxygen or in cells with few mitochondria, pyruvate is reduced to lactate in order to re-oxidize NADH back into NAD+ Pyruvate participates in several key reactions and pathways. In glycolysis, phosphoenolpyruvate (PEP) is converted to pyruvate by pyruvate kinase in an highly exergonic and irreversible reaction. In gluconeogenesis, pyruvate carboxylase and PEP carboxykinase are needed to catalyze the conversion of pyruvate to PEP. In fatty acid synthesis, the pyruvate dehydrogenase complex decarboxylates pyruvate to produce acetyl-CoA. In gluconeogenesis, the carboxylation by pyruvate carboxylase produces oxaloacetate. The fate of pyruvate depends on the cell energy charge. In cells or tissues with a high energy charge pyruvate is directed toward gluconeogenesis, but when the energy charge is low pyruvate is preferentially oxidized to CO2 and H2O in the TCA cycle, with generation of 15 equivalents of ATP per pyruvate. The enzymatic activities of the TCA cycle are located in the mitochondrion. When transported into the mitochondrion, pyruvate encounters two principal metabolizing enzymes: pyruvate carboxylase (a gluconeogenic enzyme) and pyruvate dehydrogenase (PDH). With a high cell-energy charge, acetyl-CoA, is able allosterically to activate pyruvate carboxylase, directing pyruvate toward gluconeogenesis. When the energy charge is low CoA is not acylated, pyruvate carboxylase is inactive, and pyruvate is preferentially metabolized via the PDH complex and the enzymes of the TCA cycle to CO2 and H2O.

The reaction of pyruvate to cytochrome bd terminal oxidase electron transfer starts with 2 pyruvate and 2 water molecules reacting in a pyruvate oxidase resulting in the release of 4 electrons into the inner membrane, and releasing 2 carbon dioxide molecules , 2 acetate and 4 hydrogen ion into the cytosol. 2 ubiquinone,4 hydrogen ion and 4 electron ion react resulting in the release of 2 ubiquinol . The 2 ubiquinol in turn release 4 hydrogen ions into the periplasmic space through a cytochrome bd-I terminal oxidase and releasing 4 electrons through the enzyme. Oxygen and 4 hydrogen ion reacts with the 4 electrons resulting in 2 water molecules.

The reaction of pyruvate to cytochrome bd terminal oxidase electron transfer starts with 2 pyruvate and 2 water molecules reacting in a pyruvate oxidase resulting in the release of 4 electrons into the inner membrane, and releasing 2 carbon dioxide molecules , 2 acetate and 4 hydrogen ion into the cytosol. 2 ubiquinone,4 hydrogen ion and 4 electron ion react resulting in the release of 2 ubiquinol . The 2 ubiquinol in turn release 4 hydrogen ions into the periplasmic space through a cytochrome bd-I terminal oxidase and releasing 4 electrons through the enzyme. Oxygen and 4 hydrogen ion reacts with the 4 electrons resulting in 2 water molecules.