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evolution
significant evolutionary distance existing between the type I and type II isoenzymes in Gram-negative bacteria
evolution
14 putative pyruvate kinase genes are encoded by the Arabidopsis thaliana genome. Determination of five cytosol-localized pyruvate kinases, out of the fourteen putative pyruvate kinase genes encoded by the Arabidopsis thaliana genome, phylogenetic analysis. The five identified cytosolic pyruvate kinase isoforms adjust the carbohydrate flux through the glycolytic pathway in Arabidopsis thaliana, by distinct regulatory qualities, such as individual expression pattern as well as dissimilar responsiveness to allosteric effectors and enzyme subgroup association
evolution
although Corynebacterium glutamicum is assumed to possess only one Pyk (pyk1, NCgl2008), NCgl2809 is annotated as a pyruvate kinase with an unknown role. NCgl2809 is identified as encoding pyruvate kinase (pyk2) in Corynebacterium glutamicum
evolution
enzyme EhPyk is the shortest Pyk known to date as it contains only two of the three characterized domains when compared to the other homologues, phylogenetic analysis, the enzyme belongs to a distinct branch from the known type I/II Pyks
evolution
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although Corynebacterium glutamicum is assumed to possess only one Pyk (pyk1, NCgl2008), NCgl2809 is annotated as a pyruvate kinase with an unknown role. NCgl2809 is identified as encoding pyruvate kinase (pyk2) in Corynebacterium glutamicum
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evolution
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significant evolutionary distance existing between the type I and type II isoenzymes in Gram-negative bacteria
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evolution
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although Corynebacterium glutamicum is assumed to possess only one Pyk (pyk1, NCgl2008), NCgl2809 is annotated as a pyruvate kinase with an unknown role. NCgl2809 is identified as encoding pyruvate kinase (pyk2) in Corynebacterium glutamicum
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evolution
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although Corynebacterium glutamicum is assumed to possess only one Pyk (pyk1, NCgl2008), NCgl2809 is annotated as a pyruvate kinase with an unknown role. NCgl2809 is identified as encoding pyruvate kinase (pyk2) in Corynebacterium glutamicum
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evolution
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although Corynebacterium glutamicum is assumed to possess only one Pyk (pyk1, NCgl2008), NCgl2809 is annotated as a pyruvate kinase with an unknown role. NCgl2809 is identified as encoding pyruvate kinase (pyk2) in Corynebacterium glutamicum
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evolution
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although Corynebacterium glutamicum is assumed to possess only one Pyk (pyk1, NCgl2008), NCgl2809 is annotated as a pyruvate kinase with an unknown role. NCgl2809 is identified as encoding pyruvate kinase (pyk2) in Corynebacterium glutamicum
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evolution
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although Corynebacterium glutamicum is assumed to possess only one Pyk (pyk1, NCgl2008), NCgl2809 is annotated as a pyruvate kinase with an unknown role. NCgl2809 is identified as encoding pyruvate kinase (pyk2) in Corynebacterium glutamicum
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malfunction
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erythrocytes from individuals with pyruvate kinase deficiency are resistant to invasion by Plasmodium falciparum parasites, and erythrocytes infected with ring-stage parasites are preferentially cleared by macrophages in vitro
malfunction
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FcepsilonRI-mediated inhibition of M2-type PK is required for mast cell degranulation
malfunction
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M2-PK inhibition rescues cells from glucose starvation-induced apoptotic cell death by increasing the metabolic activity
malfunction
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pyruvate kinase deficiency provides protection against infection and replication of Plasmodium falciparum in human erythrocytes
malfunction
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pyruvate kinase-deficient Escherichia coli exhibits increased plasmid copy number and cyclic AMP levels
malfunction
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the pyruvate kinase-deficient co-isogenic mouse strain CBAPk-1slc is protected against Babesia rodhaini infection
malfunction
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consequence of PKM2 inhibition is a reduced glycolytic flux, which can be reflected by the rates of cellular glucose consumption and lactate production
malfunction
human liver pyruvate kinase shows reduced affinity for phosphoenolpyruvate several days after cell lysis because Cys436 is oxidized, an effect of aging. The side chain of residue 436 is energetically coupled to phosphoenolpyruvate binding, overview
malfunction
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missense mutations of M2-PK are described in the lymphocytes of an Indian Bloom syndrome patient. Inhibition of M2-PK isdirectly linked with the initiation of mast cell degranulation
malfunction
PKM2 inhibition accumulates all upstream glycolytic intermediates as an anabolic feed for synthesis of lipids and nucleic acids. Downregulation of the enzyme activity by either phosphorylation or dissociation into dimer blocks the pyruvate production and leads in turn to an accumulation of the synthetic precursors to activate nucleic acid and lipid biosynthesis, required for cell division. The reduced cellular ATP amount as a result of PKM2 inactivation possibly activates TIGAR protein through AMPK-p53 pathway
malfunction
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the absence of extracellular serine and glycine has a pronounced inhibitory effect on pyruvate kinase activity
malfunction
the catalytic activities of the C-terminally truncated mutant toward both phophoenolpyruvate and ADP are profoundly decreased compared to those of wild-type enzyme
malfunction
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depletion of isoform PKM2 suppresses the proliferation of Hep-G2 and Huh-7 cells and enhances the activities of the epidermal growth factor/epidermal growth factor receptor and transforming growth factorbetA1/transforming growth factor receptor signaling pathways
malfunction
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hereditary enzyme deficiency leads to chronic nonspherocytic hemolytic anemia
malfunction
aberrant growth factor signalling and oxidative stress inhibit PKM2, which results in the diversion of glucose carbons into anabolic and redox regulating pathways that are essential for cell growth and survival. Proliferating PKM2-null tumour cells have no detectable PK expression, which likely reflects an adaptation that suppresses expression of PKM1 in these tumours. Consistent with a negative role of high PK activity in tumour growth, both exogenous expression of PKM1 or pharmacological activators that overcome endogenous PKM2-inhibiting mechanisms impede tumour growth by increasing cellular PK activity, effectively rendering endogenous PKM2 into a PKM1-like enzyme
malfunction
aberrant growth factor signalling and oxidative stress inhibit PKM2, which results in the diversion of glucose carbons into anabolic and redox regulating pathways that are essential for cell growth and survival. Proliferating PKM2-null tumour cells have no detectable PK expression, which likely reflects an adaptation that suppresses expression of PKM1 in these tumours. Consistent with a negative role of high PK activity in tumour growth, both exogenous expression of PKM1 or pharmacological activators that overcome endogenous PKM2-inhibiting mechanisms impede tumour growth by increasing cellular PK activity, effectively rendering endogenous PKM2 into a PKM1-like enzyme
malfunction
allosteric site structure analysis of wild-type and mutant enzymes, overview. In the S531E variant glutamate binds in place of the 6'-phosphate of fructose-1,6-bisphosphate in the allosteric site, leading to partial allosteric activation. The structure of the D499N mutant does not provide structural evidence for the previously observed allosteric activation of the D499N variant
malfunction
complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases. Fed-batch fermentation of the pyk2-overexpressing WTDELTApyk1 strain produces 60.27 g/l of lactic acid, which is a 47% increase compared to the parent strain under oxygen deprivation
malfunction
deletion of pyk1 results in marginal Pyk activity that is below the detection limit. Complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases
malfunction
overexpression of wild-type PKM2 increases H3K9 acetylation at the CYP1A1 enhancer, whereas overexpression of the PKM2K367M mutant fails to do so, indicating that efficient histone acetylation at the CYP1A1 enhancer requires the pyruvate kinase activity of PKM2
malfunction
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skeletal muscle PK from the Richardson's ground squirrel may be regulated posttranslationally between the euthermic and torpid states, and this may inhibit PK functioning during torpor in accordance with the decrease in glycolytic rate during dormancy
malfunction
the inhibition of pyruvate kinase by Zn2+ may be responsible for the cytotoxicity of this metal by decreasing glycolytic flux
malfunction
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deletion of pyk1 results in marginal Pyk activity that is below the detection limit. Complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases
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malfunction
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complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases. Fed-batch fermentation of the pyk2-overexpressing WTDELTApyk1 strain produces 60.27 g/l of lactic acid, which is a 47% increase compared to the parent strain under oxygen deprivation
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malfunction
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the catalytic activities of the C-terminally truncated mutant toward both phophoenolpyruvate and ADP are profoundly decreased compared to those of wild-type enzyme
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malfunction
-
deletion of pyk1 results in marginal Pyk activity that is below the detection limit. Complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases
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malfunction
-
complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases. Fed-batch fermentation of the pyk2-overexpressing WTDELTApyk1 strain produces 60.27 g/l of lactic acid, which is a 47% increase compared to the parent strain under oxygen deprivation
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malfunction
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deletion of pyk1 results in marginal Pyk activity that is below the detection limit. Complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases
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malfunction
-
complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases. Fed-batch fermentation of the pyk2-overexpressing WTDELTApyk1 strain produces 60.27 g/l of lactic acid, which is a 47% increase compared to the parent strain under oxygen deprivation
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malfunction
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pyruvate kinase-deficient Escherichia coli exhibits increased plasmid copy number and cyclic AMP levels
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malfunction
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deletion of pyk1 results in marginal Pyk activity that is below the detection limit. Complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases
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malfunction
-
complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases. Fed-batch fermentation of the pyk2-overexpressing WTDELTApyk1 strain produces 60.27 g/l of lactic acid, which is a 47% increase compared to the parent strain under oxygen deprivation
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malfunction
-
deletion of pyk1 results in marginal Pyk activity that is below the detection limit. Complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases
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malfunction
-
complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases. Fed-batch fermentation of the pyk2-overexpressing WTDELTApyk1 strain produces 60.27 g/l of lactic acid, which is a 47% increase compared to the parent strain under oxygen deprivation
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malfunction
-
deletion of pyk1 results in marginal Pyk activity that is below the detection limit. Complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases
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malfunction
-
complementation of the DELTApyk1DELTApyk2 strain with the pyk2 gene restores its growth on D-ribose, which demonstrates that Pyk2 can substitute for Pyk1 in vivo. Under oxygen deprivation, pyk1 or pyk2 deficiency decreases the generation of lactic acid, and the overexpression of either pyk1 or pyk2 increases the production of lactic acid as the activity of Pyk increases. Fed-batch fermentation of the pyk2-overexpressing WTDELTApyk1 strain produces 60.27 g/l of lactic acid, which is a 47% increase compared to the parent strain under oxygen deprivation
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metabolism
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the embryonic pyruvate kinase isoform PKM2 is almost universally re-expressed in cancer and promotes aerobic glycolysis, whereas the adult isoform PKM1 promotes oxidative phosphorylation
metabolism
type-II pyruvate kinase is involved in fatty acid type-II biosynthesis
metabolism
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CDC19 or HTG2 is involved in the phenotype of high-temperature growth
metabolism
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in the absence of serine, an allosteric activator of PKM2, glycolytic efflux to lactate is significantly reduced in PKM2-expressing cells. This inhibition of PKM2 results in the accumulation of glycolytic intermediates that feed into serine synthesis. the GCN2-ATF4, general control nonderepressible 2 kinase-activating transcription factor 4, pathway collaborates with PKM2-dependent alterations in glycolytic metabolism to coordinate serine synthesis
metabolism
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low pyruvate kinase activity can drive serine and glycine biosynthesis, important link between key metabolic processes observed in cancer, namely preferential PKM2 expression, aerobic glycolysis and serine biosynthesis
metabolism
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phosphoenolpyruvate enters the aromatic amino acids biosynthesis, metabolic flux distribution and Pyk activity in wild-type strain W3110 and in modified strains VH33, VH34 and VH35, overview
metabolism
pyruvate kinase catalyzes the final step in glycolysis converting phosphoenolpyruvate to pyruvate, it is a central metabolic regulator
metabolism
pyruvate kinase catalyzes the last but rate-limiting step of glycolysis
metabolism
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pyruvate kinase is a critical protein catalyzing the final step of glycolysis, which involves the transfer of a phosphoryl group from phosphoenolpyruvate to ADP, producing pyruvate and ATP
metabolism
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pyruvate kinase is a crucial regulatory enzyme involved in glycolysis
metabolism
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pyruvate kinase isoenzyme M2 plays an important role in the control of glucose metabolism
metabolism
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pyruvate kinase M2 activates mTORC1 by phosphorylating its inhibitor AKT1S1
metabolism
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red blood cell pyruvate kinase is a key regulatory enzyme of red cell metabolism
metabolism
anaerobic fermentative metabolism of glycerol. Proteome analysis as well as enzyme assays performed in cell-free extracts demonstrate that glycerol is degraded via glyceraldehyde-3-phosphate, which is further metabolized through the lower part of glycolysis leading to formation of mainly ethanol and hydrogen
metabolism
human liver pyruvate kinase (hLPYK) catalyzes the conversion of phosphoenolpyruvate (PEP) to pyruvate through a phosphoryl transfer from PEP to ADP, generating pyruvate and ATP. In human liver, this penultimate step of glycolysis is allosterically regulated by fructose-1,6-bisphosphate (Fru-1,6-BP), an earlier intermediate of glycolysis
metabolism
mode of cancer metabolism to potentially modulate the gene expression and sustain incessant proliferation by tweaking the chromatin topography, overview
metabolism
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pyruvate kinase (PK) is a key member of the glycolytic pathway. Ground squirrel torpor during winter hibernation is characterized by numerous physiological and biochemical changes, including alterations to fuel metabolism. During torpor, many tissues switch from carbohydrate to lipid catabolism, often by regulating key enzymes within glycolytic and lipolytic pathways
metabolism
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pyruvate kinase (PK) is an essential hub protein in the interactome of MRSA. PK plays a central role in the carbohydrate metabolism. It catalyzes the final rate-limiting step in the glycolysis which converts phosphoenolpyruvate (PEP) to pyruvate under ATP formation from ADP in an irreversible process
metabolism
pyruvate kinase M2 (PKM2) and pyruvate dehydrogenase complex (PDC) regulate production of acetyl-CoA, which functions as an acetyl donor in diverse enzymatic reactions, including histone acetylation. PKM2, the E2 subunit of PDC and histone acetyltransferase p300 constitute a complex on chromatin with arylhydrocarbon receptor (AhR), a transcription factor associated with xenobiotic metabolism. All of these factors are recruited to the enhancer of AhR-target genes, in an AhR-dependent manner
metabolism
the ATP synthesis in the pathogen Entamoeba histolytica is solely dependent on the glycolysis pathway where pyruvate kinase (Pyk) catalyzes the final reaction. This reaction is essentially an irreversible step of the pathway. Pyruvate kinase has been characterized as an enzyme, which is critical for the metabolic flux control of the second half of the Embden-Meyerhof-Parnas pathway. The regulation of Pyk is essential not only for this pathway but also for all other major cellular metabolisms coordinated in the cell
metabolism
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phosphoenolpyruvate enters the aromatic amino acids biosynthesis, metabolic flux distribution and Pyk activity in wild-type strain W3110 and in modified strains VH33, VH34 and VH35, overview
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metabolism
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pyruvate kinase is a crucial regulatory enzyme involved in glycolysis
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metabolism
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pyruvate kinase (PK) is an essential hub protein in the interactome of MRSA. PK plays a central role in the carbohydrate metabolism. It catalyzes the final rate-limiting step in the glycolysis which converts phosphoenolpyruvate (PEP) to pyruvate under ATP formation from ADP in an irreversible process
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physiological function
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part of citric acid cycle
physiological function
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M2-PK is a metabolic sensor which regulates cell proliferation, cell growth and apoptotic cell death in a glucose supply-dependent manner
physiological function
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Oct-4-mediated transcriptional activity is positively regulated by PKM2
physiological function
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PKM1 expression reduces the tumorigenicity of lung cancer cells, the M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth, the switch to the M2 isoform of pyruvate kinase in tumour cells is necessary to cause the metabolic phenotype known as the Warburg effect, PKM2 knockdown is rescued by expression of PKM1 in vitro
physiological function
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PKM2 enhances the use of glycolytic intermediates for macromolecular biosynthesis and tumor growth, PKM2 can clearly contribute to the development of aerobic glycolysis and the Warburg effect
physiological function
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pyruvate kinase and annexin I expressed by nerve growth factor contributes to granule formation containing TNF-alpha as well as other mediators in mast cells, which play a major role in allergic diseases via a TrkA/ERK pathway
physiological function
pyruvate kinase plays a crucial role in the regulation of pyruvate levels as well as the level of the alternative oxidase in heterotrophic plant tissue
physiological function
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suppressor of cytokine signaling 3 interacts with M2-PK to decrease ATP production causing dendritic cell dysfunction
physiological function
-
vesicle-associated pyruvate kinase can support vesicular glutamate and other neurotransmitter uptake in the presence of its substrates
physiological function
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acquisition of ProTalpha kinase activity by M2 isozyme seems to be due to the phosphorylation of serine and threonine residues, which, besides being essential for its catalytic activity, induces a trimeric association of ProTalpha kinase. Cytosolic phosphorylation of ProTaalpha, which then migrates to the nucleus, where it influences chromatin activity
physiological function
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catalytic allosteric mechanism, overview
physiological function
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phosphoenolpyruvate is a key central metabolism intermediate that participates in glucose transport, as precursor in several biosynthetic pathways and it is involved in allosteric regulation of glycolytic enzymes
physiological function
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PKM2-expressing cells can maintain mammalian target of rapamycin complex 1 activity and proliferate in serine-depleted medium, but PKM1-expressing cells cannot. Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation upon serine depletion, mTOR is a key molecular sensor for nutrient availability and a regulator of cell growth and proliferation. PKM2 confers rsistance to proliferation arrest under serine starvation, tumor cells use serine-dependent regulation of PKM2 and GCN2 to modulate the flux of glycolytic intermediates in support of cell proliferation, overview
physiological function
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PYK plays a central role in a number of proliferative and infectious diseases
physiological function
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pyruvate kinase is a glycolytic enzyme catalyzing the ATP regenerating dephosphorylation of phosphoenolpyruvate to pyruvate. Pyruvate kinase is responsible for net ATP production within the glycolytic sequence. Besides its role as glycolytic enzyme M2-PK may also function as protein kinase
physiological function
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pyruvate kinase is a glycolytic enzyme catalyzing the ATP regenerating dephosphorylation of phosphoenolpyruvate to pyruvate. Pyruvate kinase is responsible for net ATP production within the glycolytic sequence. Besides its role as glycolytic enzyme M2-PK may also function as protein kinase. In tumor metabolism the quaternary structure of M2-PK (tetramer:dimer ratio) determines whether glucose is used for glycolytic energy regeneration (highly active tetrameric form, Warburg effect) or synthesis of cell building blocks (nearly inactive dimeric form) which are both prerequisites for cells with a high proliferation rate. In tumor cells the nearly inactive dimeric form of M2-PK is predominant due to direct interactions with different oncoproteins. Besides its key functions in tumor metabolism, M2-PK may also react as protein kinase as well as co activator of transcription factors. The mTOR/HIF-1a/c-myc/M2-PK cascade may be one explanation for the increased aerobic glycolysis in tumor cells first described by Otto Warburg, overview. Nuclear translocation of M2-PK by the somatostatin analogue TT232, H2O2 or UV light are linked to the induction of caspase independent apoptosis. M2-PK binds to the mast cell IgE receptor FcepsilonRI and plays a crucial role in responses to allergens
physiological function
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pyruvate kinase isozyme PKM2 is a rate-limiting enzyme of aerobic glycolysis in cancer cells and plays important roles in cancer metabolism and growth. Vitamin K3/vitamin K5-enhanced toxicity of doxorubicin is associated with pyruvate kinase activity
physiological function
pyruvate kinase of Cryptosporidium parvum is exceptional among known enzymes of protozoan origin in that it exhibits no allosteric property in the presence of commonly known effector molecules, mainly phosphosugars, due to blockage of the effector binding site by a sulfate ion, overview
physiological function
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pyruvate kinase triggers a metabolic feedback loop that controls redox metabolism in respiring cells. Low PYK activity activates yeast respiration, the central metabolism is self-adapting to synchronize redox metabolism when respiration is activated. A metabolic feedback loop is responsible for preventing an increase in reactive oxygen species upon respiration activation. Low PYK enzyme activity causes accumulation of phosphoenolpyruvate, which in turn inhibits triose phosphate isomerase, an enzyme of upper glycolysis. This inhibition of triose phosphate isomerase increases metabolite content of the pentose phosphate pathway, a catabolic pathway closely connected to glycolysis. The PYK-PEP-TPI feedback loop protects cells from ROS-induced damage during respiration, metabolic mechanism, overview
physiological function
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required role of the active site in allosteric regulation involving substrate binding, requirement for monovalent and divalent cations, overview
physiological function
tetrameric isozyme PKM2 is an allosterically regulated isoform and intrinsically designed to downregulate its activity by subunit dissociation from tetramer to dimer, which results in partial inhibition of glycolysis at the last step. Reassociation of PKM2 into active tetramer replenishes the normal catabolism as a feedback after cell division. PKM2 is a metabolic regulator, involvement of this enzyme in a variety of pathways, protein-protein interactions, and nuclear transport suggests its potential to perform multiple nonglycolytic functions with diverse implications, overview. Downregulation of the enzyme activity by either phosphorylation or dissociation into dimer blocks the pyruvate production and leads in turn to an accumulation of the synthetic precursors to activate nucleic acid and lipid biosynthesis, required for cell division PKM2 saves the cell from nutritional stress-dependent apoptosis during cell division process
physiological function
the C-terminal domain is not required for substrate binding or allosteric regulation observed in the holoenzyme, the kinetic efficiency of the truncated enzyme is decreased by 24 and 16fold, in ligand-free state, toward phophoenolpyruvate and ADP, respectively, but is restored by 3fold in AMP-bound state. The C-terminal domain (Gly473-Leu585) plays a substantial role in enzyme activity and comformational stability, and the C-terminal domain is involved in maintaining the specificity of allosteric regulation
physiological function
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the enzyme is involved in the modified Embden-Meyerhof pathway
physiological function
the enzyme uses a rock and lock model allosteric mechanism, intersubunit interactions on the A-A and C-C interfaces strongly influence the allosteric effect whereas mutations affecting the intrasubunit A-C interface are less sensitive, overview. Conformational changes coupled with effector binding correlate with loss of flexibility and increase in thermal stability providing a general mechanism for allosteric control
physiological function
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the expression of the M2 isozyme of pyruvate kinase plays an important role in the anabolic metabolism of cancer cells
physiological function
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the Warburg effect, a metabolic change, originates from a shift in the expression of alternative spliced isoforms of the glycolytic enzyme pyruvate kinase, from PKM1 to PKM2. While PKM1 is constitutively active, PKM2 is switched from an inactive dimer form to an active tetramer form by small molecule activators. Activation of PKM2 may counter the abnormal cellular metabolism in cancer cells, and consequently decreased cellular proliferation
physiological function
the enzyme catalyzes the final step of glycolysis
physiological function
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the enzyme is involved in glycogen catabolism
physiological function
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isoform PKM2 plasy different roles in modulating the proliferation and metastasis of hepatocellular carcinoma cells
physiological function
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the conversion between the pyruvate kinase and protein kinase activities of PKM2 are an important mechanism mediating the effects of growth signals in promoting cell proliferation
physiological function
allosteric regulation of trypanosomatid PYKs, overview
physiological function
allosteric regulation of trypanosomatid PYKs, overview
physiological function
cytosolic PK is a key player in energy allocation, as it generates ATP in the cytosol, supplies pyruvate to the TCA cycle and thereby drives mitochondrial ATP synthesis. The cytosolic pyruvate kinase (cPK) represents a key glycolytic enzyme by catalyzing phosphate transfer from phosphoenolpyruvate (PEP) to ADP for the synthesis of ATP. Besides its important functions in cellular energy homeostasis, the activity of cytosolic pyruvate kinase underlies tight regulation, for instance by allosteric effectors, that impact stability of its quaternary structure. The five identified cytosolic pyruvate kinase isoforms adjust the carbohydrate flux through the glycolytic pathway in Arabidopsis thaliana, by distinct regulatory qualities, such as individual expression pattern as well as dissimilar responsiveness to allosteric effectors and enzyme subgroup association
physiological function
cytosolic PK is a key player in energy allocation, as it generates ATP in the cytosol, supplies pyruvate to the TCA cycle and thereby drives mitochondrial ATP synthesis. The cytosolic pyruvate kinase (cPK) represents a key glycolytic enzyme by catalyzing phosphate transfer from phosphoenolpyruvate (PEP) to ADP for the synthesis of ATP. Besides its important functions in cellular energy homeostasis, the activity of cytosolic pyruvate kinase underlies tight regulation, for instance by allosteric effectors, that impact stability of its quaternary structure. The five identified cytosolic pyruvate kinase isoforms adjust the carbohydrate flux through the glycolytic pathway in Arabidopsis thaliana, by distinct regulatory qualities, such as individual expression pattern as well as dissimilar responsiveness to allosteric effectors and enzyme subgroup association. Spatial distribution of glycolytic enzymes within the cell constitutes a further point of regulation, since enzymes may localize at sites of demand for glycolytic intermediates
physiological function
human liver pyruvate kinase (hLPYK) converts phosphoenolpyruvate to pyruvate in the final step of glycolysis. hLPYK is allosterically activated by fructose-1,6-bisphosphate (Fru-1,6-BP)
physiological function
human pyruvate kinase isoform M2 (PKM2) is a glycolytic enzyme isoform implicated in cancer. Malignant cancer cells have higher levels of dimeric PKM2, which is regarded as an inactive form of tetrameric pyruvate kinase. The enzymatic activity of the PKM2 dimer likely has a key role in cancer progression. In addition to its classical role in generating ATP from ADP and the phosphate donor PEP, PKM2 also has been found to phosphorylate protein substrates
physiological function
PKM2 is recruited to gene enhancers of the AhR-target genes in an AhR-dependent manner and promotes AhR transactivation. Pyruvate kinase M2 (PKM2) and pyruvate dehydrogenase complex (PDC) regulate production of acetyl-CoA, which functions as an acetyl donor in diverse enzymatic reactions, including histone acetylation. PKM2, the E2 subunit of PDC and histone acetyltransferase p300 constitute a complex on chromatin with arylhydrocarbon receptor (AhR), a transcription factor associated with xenobiotic metabolism. All of these factors, also PKM2, are recruited to the enhancer of AhR-target genes, in an AhR-dependent manner. PKM2 contributes to enhancement of transcription of cytochrome P450 1A1 (CYP1A1), an AhR-target gene, acetylation at lysine 9 of histone H3 at the CYP1A1 enhancer. A local acetyl-CoA production system is proposed in which PKM2 and PDC locally supply acetyl-CoA to p300 from abundant PEP for histone acetylation at the gene enhancer. PKM2 sensitizes AhR-mediated detoxification in actively proliferating cells such as cancer and fetal cells
physiological function
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pyruvate kinase (PK) is an essential hub protein in the interactome of MRSA. PK plays a central role in the carbohydrate metabolism. It catalyzes the final rate-limiting step in the glycolysis which converts phosphoenolpyruvate (PEP) to pyruvate under ATP formation from ADP in an irreversible process
physiological function
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pyruvate kinase (PK) is responsible for catalyzing the final step of glycolysis, which involves the transfer of the phosphoryl group of phosphoenolpyruvate (PEP) to ADP to produce pyruvate and ATP. Pyruvate kinase has been identified as a highly interconnected essential hub protein in methicillin-resistant Staphylococcus aureus (MRSA), with structural features distinct from the human homologues
physiological function
pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection
physiological function
pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection. Pyk2 functions as a pyruvate kinase and contributes to the increased level of Pyk activity under oxygen deprivation. The catalytic activity of Pyk2 is allosterically regulated by fructose 1,6-bisphosphate activation and ATP inhibition
physiological function
pyruvate kinase enzyme catalyzes the last rate-limiting step of glycolysis converting phosphoenolpyruvate to pyruvate with the subsequent production of ATP. Pyruvate kinase M2 (PKM2) is an oncofetal isoform generated as a result of alternative splicing of the PKM mRNA transcript exhibit low basal activity and thus is a key player in regulating the glycolytic flux contributing to cancer progression. It results in the build-up of glycolytic intermediates which are directed towards the biosynthetic processes. PKM2 mediates metabolic reshuffling and is ubiquitously upregulated in several cancer types. The non-metabolic function of PKM2 as key nuclear kinase and modulator of gene expression is instrumental in cancer progression and tumorigenesis. The non-canonical function of PKM2 is an epigenetic modulator. Enzyme PKM2 interacts with the reconstituted mononucleosome complex through histone H3 and possibly obstructs the access to DNA binding factors. The interaction negatively impacts the ATP-dependent remodeling activity of chromodomain helicase DNA binding protein-7 (Chd7). Chd7 remodeling activity is required to ameliorate DNA damage and is crucial to genome stability. PKM2 blocks the Chd7 mediated sliding of nucleosome. It can be conjectured that stalling Chd7 may lead to impaired DNA damage and increased genomic instability. PKM2 negatively regulates nucleosome repositioning in chromatin and may exacerbate cancer by altering the nucleosome architecture, mechanism, overview. The nucleosome digestion activity of the PKM2-nucleosome complex is remarkably impaired as can be inferred from the digestion profile. Pyruvate kinase M2 can potentially disrupt the ChD7-mediated remodeling of nucleosome
physiological function
pyruvate kinase M2 (PKM2) is a rate-limiting enzyme of the glycolytic pathway which is highly expressed in cancer cells. Cancer cells rely heavily on PKM2 for anabolic and energy requirements
physiological function
pyruvate kinase M2 isoform (PKM2) is a crucial protein responsible for aerobic glycolysis of cancer cells. Activation of PKM2 may alter an aberrant metabolism in cancer cells
physiological function
pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme involved in ATP generation and critical for cancer metabolism. PKM2 is expressed in many human cancers and is regulated by complex mechanisms that promote tumor growth and proliferation. Amino acids are involved in regulation of pyruvate kinase muscle isoform 2, overview. Various stimuli allosterically regulate PKM2 by cycling it between highly active and less active states. Several small molecules activate PKM2 by binding to its intersubunit interface. Despite binding similarly to PKM2, cysteine and serine differentially regulate the enzyme
physiological function
relationship between pyruvate kinase activity and cariogenic biofilm formation in Streptococcus mutans biotypes in caries patients, analysis of pyruvate kinase activity with respect to caries severity, statistical analysis, overview
physiological function
The prolyl hydroxylase 3 (PHD3, EC 1.14.11.29) protein is less abundant in normal oxygen conditions (normoxia) but increases under deficient oxygen condition (hypoxia). Since cancerous cells often thrive in hypoxic conditions and predominantly express the pyruvate kinase isoforms 2 (PKM2), the PHD3/PKM2 interaction might be particularly important in cancer development. Protein interaction analysis and PHD3/PKM2 complex structure analysis, overview. PHD3 hydroxylates the PKM2 at two specific proline residues. The hydroxylated PKM2 shows enhanced binding with HIF-1alpha, which in turn increases the activity of HIF-1alpha
physiological function
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the skeletal muscle pyruvate kinase from the hibernating ground squirrel shows potential regulation by posttranslational modification during torpor. Torpid pyruvate kinase (PK) displays a nearly threefold increase in Km PEP as compared to control PK when assayed at 5°C. Torpid PK is significantly more phosphorylated than the euthermic control. PK from the torpid condition is also shown to possess nearly twofold acetyl content as compared to control PK
physiological function
various intracellular mechanisms in cancer cells maintain PKM2 in a low-activity monomeric state and forced stabilisation of tetrameric PKM2 increases its enzymatic activity thereby impeding cell proliferation
physiological function
various intracellular mechanisms in cancer cells maintain PKM2 in a low-activity monomeric state and forced stabilisation of tetrameric PKM2 increases its enzymatic activity thereby impeding cell proliferation
physiological function
Vibrio cholerae has two isozymes that contribute to the pyruvate kinase activity: one K+-dependent constitutively active isozyme and another K+-independent isozyme with essential allosteric activation. The pyruvate kinase isozyme sequences with Glu117 have been found to be K+-dependent, whereas those with Lys117 are K+-independent
physiological function
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pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection
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physiological function
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pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection. Pyk2 functions as a pyruvate kinase and contributes to the increased level of Pyk activity under oxygen deprivation. The catalytic activity of Pyk2 is allosterically regulated by fructose 1,6-bisphosphate activation and ATP inhibition
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physiological function
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the C-terminal domain is not required for substrate binding or allosteric regulation observed in the holoenzyme, the kinetic efficiency of the truncated enzyme is decreased by 24 and 16fold, in ligand-free state, toward phophoenolpyruvate and ADP, respectively, but is restored by 3fold in AMP-bound state. The C-terminal domain (Gly473-Leu585) plays a substantial role in enzyme activity and comformational stability, and the C-terminal domain is involved in maintaining the specificity of allosteric regulation
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physiological function
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pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection
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physiological function
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pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection. Pyk2 functions as a pyruvate kinase and contributes to the increased level of Pyk activity under oxygen deprivation. The catalytic activity of Pyk2 is allosterically regulated by fructose 1,6-bisphosphate activation and ATP inhibition
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physiological function
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the enzyme catalyzes the final step of glycolysis
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physiological function
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phosphoenolpyruvate is a key central metabolism intermediate that participates in glucose transport, as precursor in several biosynthetic pathways and it is involved in allosteric regulation of glycolytic enzymes
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physiological function
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pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection
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physiological function
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pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection. Pyk2 functions as a pyruvate kinase and contributes to the increased level of Pyk activity under oxygen deprivation. The catalytic activity of Pyk2 is allosterically regulated by fructose 1,6-bisphosphate activation and ATP inhibition
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physiological function
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pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection
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physiological function
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pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection. Pyk2 functions as a pyruvate kinase and contributes to the increased level of Pyk activity under oxygen deprivation. The catalytic activity of Pyk2 is allosterically regulated by fructose 1,6-bisphosphate activation and ATP inhibition
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physiological function
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Vibrio cholerae has two isozymes that contribute to the pyruvate kinase activity: one K+-dependent constitutively active isozyme and another K+-independent isozyme with essential allosteric activation. The pyruvate kinase isozyme sequences with Glu117 have been found to be K+-dependent, whereas those with Lys117 are K+-independent
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physiological function
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pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection
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physiological function
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pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection. Pyk2 functions as a pyruvate kinase and contributes to the increased level of Pyk activity under oxygen deprivation. The catalytic activity of Pyk2 is allosterically regulated by fructose 1,6-bisphosphate activation and ATP inhibition
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physiological function
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pyruvate kinase (PK) is responsible for catalyzing the final step of glycolysis, which involves the transfer of the phosphoryl group of phosphoenolpyruvate (PEP) to ADP to produce pyruvate and ATP. Pyruvate kinase has been identified as a highly interconnected essential hub protein in methicillin-resistant Staphylococcus aureus (MRSA), with structural features distinct from the human homologues
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physiological function
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allosteric regulation of trypanosomatid PYKs, overview
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physiological function
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Vibrio cholerae has two isozymes that contribute to the pyruvate kinase activity: one K+-dependent constitutively active isozyme and another K+-independent isozyme with essential allosteric activation. The pyruvate kinase isozyme sequences with Glu117 have been found to be K+-dependent, whereas those with Lys117 are K+-independent
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physiological function
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pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection
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physiological function
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pyruvate kinase (Pyk) catalyzes the generation of pyruvate and ATP in glycolysis and functions as a key switch in the regulation of carbon flux distribution. Both the substrates and products of Pyk are involved in the tricarboxylic acid cycle, anaplerosis and energy anabolism, which places Pyk at a primary metabolic intersection. Pyk2 functions as a pyruvate kinase and contributes to the increased level of Pyk activity under oxygen deprivation. The catalytic activity of Pyk2 is allosterically regulated by fructose 1,6-bisphosphate activation and ATP inhibition
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physiological function
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pyruvate kinase (PK) is an essential hub protein in the interactome of MRSA. PK plays a central role in the carbohydrate metabolism. It catalyzes the final rate-limiting step in the glycolysis which converts phosphoenolpyruvate (PEP) to pyruvate under ATP formation from ADP in an irreversible process
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additional information
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allosteric mechanism of rM1-PYK, overview
additional information
allosteric site structure and regulation, overview. Comparison of the B domain open and closed conformation shows reorientation of the monomers with a concomitant change in the buried surface among adjacent monomers. The change in the buried surface is associated with significant B domain movements in one of the interacting monomers. A loop in the interface between the A and B domains plays an important role linking the position of the B domain to the buried surface among monomers through two alpha-helices. An unusual ordered conformation is observed in one of the allosteric binding domains, it is related to a specific apicomplexan insertion
additional information
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allosteric site structure and regulation, overview. Comparison of the B domain open and closed conformation shows reorientation of the monomers with a concomitant change in the buried surface among adjacent monomers. The change in the buried surface is associated with significant B domain movements in one of the interacting monomers. A loop in the interface between the A and B domains plays an important role linking the position of the B domain to the buried surface among monomers through two alpha-helices. An unusual ordered conformation is observed in one of the allosteric binding domains, it is related to a specific apicomplexan insertion
additional information
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catalysis by muscle pyruvate kinase involves domain movements and conformational changes induced by activating cations and its substrates. Fluorescence acrylamide quenching analyses reveal that interactions with Mg2+ and K+ lead to a more exposed active site of the enzyme while interactions with phosphoenolpyruvate and ADP decrease solvent accessibility of the active site, overview
additional information
energetic coupling between an oxidizable cysteine and the phosphorylatable N-terminus of human liver pyruvate kinase determines substrate affinity and activity, overview. Oxidation of Cys436 and phosphorylation of the N-terminus at Ser12 may function through a similar mechanism, namely the interruption of an activating interaction between the nonphosphorylated N-terminus with the nonoxidized main body of the protein. Modeling of C436M-L-PYK-citrate-Mn-ATP-Fru-1,6-bisphosphate complex using crystal structure of S12D mutant in a S12D-L-PYK-Fru-1,6-bisphosphate-Mn-Na-citrate complex, overview
additional information
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energetic coupling between an oxidizable cysteine and the phosphorylatable N-terminus of human liver pyruvate kinase determines substrate affinity and activity, overview. Oxidation of Cys436 and phosphorylation of the N-terminus at Ser12 may function through a similar mechanism, namely the interruption of an activating interaction between the nonphosphorylated N-terminus with the nonoxidized main body of the protein. Modeling of C436M-L-PYK-citrate-Mn-ATP-Fru-1,6-bisphosphate complex using crystal structure of S12D mutant in a S12D-L-PYK-Fru-1,6-bisphosphate-Mn-Na-citrate complex, overview
additional information
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expression of M2-PK is under the control of nutrients, insulin, different transcription factors such as SP1, SP3, HIF-1alpha, as well as c-myc, the zonula occludens protein 2 (ZO-2), Ras and microRNA 133a and 133b
additional information
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movement of the B domain is essential for the catalytic reaction. Rotation of the B domain in the opening of the cleft between domains B and A induced by the binding of activating cations allows substrates to bind, whereas substrate binding shifts the rotation of the B domain in the closure of the cleft. The enzyme exhibits a more dynamic structure after binding of activating metal ions and substrates, whereas binding of Phe decreases the dynamics
additional information
the C-terminally truncated enzyme exhibits high affinity toward both phophoenolpyruvate and ADP and exhibits hyperbolic kinetics toward phophoenolpyruvate in the presence of activators AMP and ribose 5-phosphate consistent with kinetic properties of full-length enzyme
additional information
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the C-terminally truncated enzyme exhibits high affinity toward both phophoenolpyruvate and ADP and exhibits hyperbolic kinetics toward phophoenolpyruvate in the presence of activators AMP and ribose 5-phosphate consistent with kinetic properties of full-length enzyme
additional information
the partially closed active site structure contains an alpha6' helix that unwinds and assumes an extended conformation, a glycerol molecule is located near the gamma-phosphate site of ATP. A sulfate ion is found at a site that is occupied by a phosphate of the effector molecule
additional information
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the partially closed active site structure contains an alpha6' helix that unwinds and assumes an extended conformation, a glycerol molecule is located near the gamma-phosphate site of ATP. A sulfate ion is found at a site that is occupied by a phosphate of the effector molecule
additional information
the transition between inactive T-state and active R-state is accompanied by a simple symmetrical 6o rigid body rocking motion of the A- and C-domain cores in each of the four subunits. Eight essential salt bridge locks form across the C-C interface providing tetramer rigidity with a coupled 7fold increase in reaction rate
additional information
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the transition between inactive T-state and active R-state is accompanied by a simple symmetrical 6o rigid body rocking motion of the A- and C-domain cores in each of the four subunits. Eight essential salt bridge locks form across the C-C interface providing tetramer rigidity with a coupled 7fold increase in reaction rate
additional information
amino acid-bound crystal structures of PKM2 display distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. Structure-function analyses of amino acid-mediated PKM2 regulation, overview, revealing the chemical requirements in the development of mechanism-based small-molecule modulators targeting the amino acid-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzyme
additional information
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amino acid-bound crystal structures of PKM2 display distinctive interactions within the binding pocket, causing unique allosteric effects in the enzyme. Structure-function analyses of amino acid-mediated PKM2 regulation, overview, revealing the chemical requirements in the development of mechanism-based small-molecule modulators targeting the amino acid-binding pocket of PKM2 and provide broader insights into the regulatory mechanisms of complex allosteric enzyme
additional information
analysis of structure-function relationships of pyruvate kinases (PYKs) from trypanosomatids (Trypanosoma and Leishmania), especially of TcoPYK (Uniprot ID G0UYF4) and TbrPYK (Uniprot ID P30615), overview. Substrate binding causes several structural rearrangements across the entire PYK tetramer that involve (i) AC-core rotation of 6-8° (with residues 430-434 as a pivot point), (ii) closing of the lid domain (rotation of 30-40°), (iii) stabilization of the AA' dimer interfaces, and (iv) flipping of the Arg311 side chain as part of remodeling the catalytic pocket for substrate accommodation
additional information
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analysis of structure-function relationships of pyruvate kinases (PYKs) from trypanosomatids (Trypanosoma and Leishmania), especially of TcoPYK (Uniprot ID G0UYF4) and TbrPYK (Uniprot ID P30615), overview. Substrate binding causes several structural rearrangements across the entire PYK tetramer that involve (i) AC-core rotation of 6-8° (with residues 430-434 as a pivot point), (ii) closing of the lid domain (rotation of 30-40°), (iii) stabilization of the AA' dimer interfaces, and (iv) flipping of the Arg311 side chain as part of remodeling the catalytic pocket for substrate accommodation
additional information
analysis of structure-function relationships of pyruvate kinases (PYKs) from trypanosomatids (Trypanosoma and Leishmania), especially of TcoPYK (Uniprot ID G0UYF4) and TbrPYK (Uniprot ID P30615), overview. Substrate binding causes several structural rearrangements across the entire PYK tetramer that involve (i) AC-core rotation of 6-8° (with residues 430-434 as a pivot point), (ii) closing of the lid domain (rotation of 30-40°), (iii) stabilization of the AA' dimer interfaces, and (iv) flipping of the Arg311 side chain as part of remodeling the catalytic pocket for substrate accommodation
additional information
changes in the allosteric site of human liver pyruvate kinase upon activator binding include the breakage of an intersubunit cation-Pi bond. Conformational toggle between the open and closed positions of the allosteric loop, structure analysis of wild-type and mutant enzymes, overview. In the absence of fructose-1,6-bisphosphate the open position is stabilized, in part, by a cation-Pi bond between Trp527 and Arg538' (from an adjacent monomer). In the S531E variant glutamate binds in place of the 6'-phosphate of fructose-1,6-bisphosphate in the allosteric site, leading to partial allosteric activation. The structure of the D499N mutant does not provide structural evidence for the previously observed allosteric activation of the D499N variant
additional information
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changes in the allosteric site of human liver pyruvate kinase upon activator binding include the breakage of an intersubunit cation-Pi bond. Conformational toggle between the open and closed positions of the allosteric loop, structure analysis of wild-type and mutant enzymes, overview. In the absence of fructose-1,6-bisphosphate the open position is stabilized, in part, by a cation-Pi bond between Trp527 and Arg538' (from an adjacent monomer). In the S531E variant glutamate binds in place of the 6'-phosphate of fructose-1,6-bisphosphate in the allosteric site, leading to partial allosteric activation. The structure of the D499N mutant does not provide structural evidence for the previously observed allosteric activation of the D499N variant
additional information
comparisons of isozyme PYK-I structures in the active R-state and inactive T-state reveal a rock-and-lock allosteric mechanism regulated by rigid-body rotations of each subunit in the tetramer. It is likely that the GST-tag on the recombinant enzyme partially hinders or affects conformational changes occurring in the PfPYK-I tetramer, which are crucial for allosteric regulation. Structure-function analysis, overview
additional information
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comparisons of isozyme PYK-I structures in the active R-state and inactive T-state reveal a rock-and-lock allosteric mechanism regulated by rigid-body rotations of each subunit in the tetramer. It is likely that the GST-tag on the recombinant enzyme partially hinders or affects conformational changes occurring in the PfPYK-I tetramer, which are crucial for allosteric regulation. Structure-function analysis, overview
additional information
homology modelling of EhPyk, molecular dynamics simulation study
additional information
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homology modelling of EhPyk, molecular dynamics simulation study
additional information
molecular dynamics (MD) simulations of the human PKM2 (hPKM2) monomer in the absence (apo-hPKM2) or presence of FBP (hPKM2-FBP), analysis of the mechanical response of PKM2 upon binding of FBP, overview
additional information
the isozymes cPK1-5 show positive, synergistic effects when mixed
additional information
the isozymes cPK1-5 show positive, synergistic effects when mixed
additional information
the isozymes cPK1-5 show positive, synergistic effects when mixed
additional information
the isozymes cPK1-5 show positive, synergistic effects when mixed
additional information
the isozymes cPK1-5 show positive, synergistic effects when mixed
additional information
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the isozymes cPK1-5 show positive, synergistic effects when mixed
additional information
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the C-terminally truncated enzyme exhibits high affinity toward both phophoenolpyruvate and ADP and exhibits hyperbolic kinetics toward phophoenolpyruvate in the presence of activators AMP and ribose 5-phosphate consistent with kinetic properties of full-length enzyme
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additional information
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analysis of structure-function relationships of pyruvate kinases (PYKs) from trypanosomatids (Trypanosoma and Leishmania), especially of TcoPYK (Uniprot ID G0UYF4) and TbrPYK (Uniprot ID P30615), overview. Substrate binding causes several structural rearrangements across the entire PYK tetramer that involve (i) AC-core rotation of 6-8° (with residues 430-434 as a pivot point), (ii) closing of the lid domain (rotation of 30-40°), (iii) stabilization of the AA' dimer interfaces, and (iv) flipping of the Arg311 side chain as part of remodeling the catalytic pocket for substrate accommodation
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