Preferred Name | Gluconeogenesis | |
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Definitions |
The reactions of gluconeogenesis convert mitochondrial pyruvate to cytosolic glucose 6-phosphate which in turn can be hydrolyzed to glucose and exported from the cell. Gluconeogenesis is confined to cells of the liver and kidney and enables glucose synthesis from molecules such as lactate and alanine and other amino acids when exogenous glucose is not available (reviewed, e.g., by Gerich 1993). The process of gluconeogenesis as diagrammed below occurs in two parts: a network of reactions converts mitochondrial pyruvate to cytosolic phosphoenolpyruvate; then phosphoenolpyruvate is converted to glucose 6-phosphate in a single sequence of cytosolic reactions.<p>Three variants of the first part of the process are physiologically important. 1) A series of transport and transamination reactions convert mitochondrial oxaloacetate to cytosolic oxaloacetate which is converted to phosphoenolpyruvate by a hormonally regulated, cytosolic isoform of phosphoenolpyruvate carboxykinase. This variant allows regulated glucose synthesis from lactate. 2) Mitochondrial oxaloacetate is reduced to malate, which is exported to the cytosol and re-oxidized to oxaloacetate. This variant provides reducing equivalents to the cytosol, needed for glucose synthesis from amino acids such as alanine and glutamine. 3) Constitutively expressed mitochondrial phosphoenolpyruvate carboxykinase catalyzes the conversion of mitochondrial oxaloacetate to phosphoenolpyruvate which is then transported to the cytosol. The exact path followed by any one molecule of pyruvate through this reaction network is determined by the tissue in which the reactions are occurring, the source of the pyruvate, and the physiological stress that triggered gluconeogenesis.<p>In all cases, the synthesis of glucose from two molecules of pyruvate requires the generation and consumption of two reducing equivalents as cytosolic NADH + H+. For pyruvate derived from lactate (variants 1 and 3), NADH + H+ is generated with the oxidation of lactate to pyruvate in the cytosol (a reaction of pyruvate metabolism not shown in the diagram). For pyruvate derived from amino acids (variant 2), mitochondrial NADH + H+ generated by glutamate dehydrogenase (a reaction of amino acid metabolism, not shown) is used to reduce oxaloacetate to malate, which is transported to the cytosol and re-oxidized, generating cytosolic NADH + H+. The synthesis of glucose from pyruvate also requires the consumption of six high-energy phosphates, four from ATP and two from GTP.<p>In the second part of gluconeogenesis, cytosolic phosphoenolpyruvate, however derived, is converted to fructose 1,6-bisphosphate by reactions that are the reverse of steps of glycolysis. Hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate is catalyzed by fructose 1,6-bisphosphatase, and fructose 6-phosphate is reversibly isomerized to glucose 6-phosphate. Reviewed: Harris, RA, 2008-09-10 18:47:12 Edited: D'Eustachio, P, 0000-00-00 00:00:00 |
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ID |
http://purl.obolibrary.org/obo/HINO_0015270 |
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comment |
The reactions of gluconeogenesis convert mitochondrial pyruvate to cytosolic glucose 6-phosphate which in turn can be hydrolyzed to glucose and exported from the cell. Gluconeogenesis is confined to cells of the liver and kidney and enables glucose synthesis from molecules such as lactate and alanine and other amino acids when exogenous glucose is not available (reviewed, e.g., by Gerich 1993). The process of gluconeogenesis as diagrammed below occurs in two parts: a network of reactions converts mitochondrial pyruvate to cytosolic phosphoenolpyruvate; then phosphoenolpyruvate is converted to glucose 6-phosphate in a single sequence of cytosolic reactions. Three variants of the first part of the process are physiologically important. 1) A series of transport and transamination reactions convert mitochondrial oxaloacetate to cytosolic oxaloacetate which is converted to phosphoenolpyruvate by a hormonally regulated, cytosolic isoform of phosphoenolpyruvate carboxykinase. This variant allows regulated glucose synthesis from lactate. 2) Mitochondrial oxaloacetate is reduced to malate, which is exported to the cytosol and re-oxidized to oxaloacetate. This variant provides reducing equivalents to the cytosol, needed for glucose synthesis from amino acids such as alanine and glutamine. 3) Constitutively expressed mitochondrial phosphoenolpyruvate carboxykinase catalyzes the conversion of mitochondrial oxaloacetate to phosphoenolpyruvate which is then transported to the cytosol. The exact path followed by any one molecule of pyruvate through this reaction network is determined by the tissue in which the reactions are occurring, the source of the pyruvate, and the physiological stress that triggered gluconeogenesis. In all cases, the synthesis of glucose from two molecules of pyruvate requires the generation and consumption of two reducing equivalents as cytosolic NADH + H+. For pyruvate derived from lactate (variants 1 and 3), NADH + H+ is generated with the oxidation of lactate to pyruvate in the cytosol (a reaction of pyruvate metabolism not shown in the diagram). For pyruvate derived from amino acids (variant 2), mitochondrial NADH + H+ generated by glutamate dehydrogenase (a reaction of amino acid metabolism, not shown) is used to reduce oxaloacetate to malate, which is transported to the cytosol and re-oxidized, generating cytosolic NADH + H+. The synthesis of glucose from pyruvate also requires the consumption of six high-energy phosphates, four from ATP and two from GTP. In the second part of gluconeogenesis, cytosolic phosphoenolpyruvate, however derived, is converted to fructose 1,6-bisphosphate by reactions that are the reverse of steps of glycolysis. Hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate is catalyzed by fructose 1,6-bisphosphatase, and fructose 6-phosphate is reversibly isomerized to glucose 6-phosphate. Reviewed: Harris, RA, 2008-09-10 18:47:12 Edited: D'Eustachio, P, 0000-00-00 00:00:00 |
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definition source |
Reactome, http://www.reactome.org Pubmed8379904 |
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label |
Gluconeogenesis |
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located_in | ||
prefixIRI |
HINO:0015270 |
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prefLabel |
Gluconeogenesis |
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seeAlso |
ReactomeREACT_1520 Reactome Database ID Release 4370263 GENE ONTOLOGYGO:0006094 |
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subClassOf | ||
has_part |
http://purl.obolibrary.org/obo/HINO_0019370 http://purl.obolibrary.org/obo/HINO_0019376 http://purl.obolibrary.org/obo/HINO_0019372 http://purl.obolibrary.org/obo/HINO_0019375 http://purl.obolibrary.org/obo/HINO_0019377 http://purl.obolibrary.org/obo/HINO_0019374 http://purl.obolibrary.org/obo/HINO_0019625 http://purl.obolibrary.org/obo/HINO_0019629 http://purl.obolibrary.org/obo/HINO_0019622 http://purl.obolibrary.org/obo/HINO_0019623 http://purl.obolibrary.org/obo/HINO_0019626 http://purl.obolibrary.org/obo/HINO_0019628 http://purl.obolibrary.org/obo/HINO_0019630 http://purl.obolibrary.org/obo/HINO_0019631 http://purl.obolibrary.org/obo/HINO_0019368 http://purl.obolibrary.org/obo/HINO_0019367 http://purl.obolibrary.org/obo/HINO_0019354 http://purl.obolibrary.org/obo/HINO_0019355 http://purl.obolibrary.org/obo/HINO_0019340 |