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Enzyme Nomenclature
Information on EC 2.7.1.40 - pyruvate kinase
for references in articles please use BRENDA:EC2.7.1.40
Word Map on EC 2.7.1.40
- 2.7.1.40
- lactate
- hexokinase
-
phosphofructokinase
- erythrocyte
- fructose
- glucose-6-phosphate
- hepatocytes
- anemia
- glycogen
- pep
-
aldolase
-
gluconeogenesis
-
carboxykinase
- malate
- citrate
-
hemolytic
- creatine
- diabetes
- glucokinase
-
gluconeogenic
- glucagon
- 6-phosphate
- adenylate
- enolase
- phosphoglycerate
-
warburg
-
malic
- pentose
- glyceraldehyde-3-phosphate
-
lipogenesis
- 6-phosphogluconate
- fructose-1,6-bisphosphate
- isocitrate
- reticulocyte
-
liver-type
- triose
-
lipogenic
- fructose-6-phosphate
-
splenectomy
- 2,3-diphosphoglycerate
-
1,6-bisphosphatase
-
triosephosphate
- 2,6-bisphosphate
-
glycogenolysis
-
reticulocytosis
- drug development
- diagnostics
-
heterotropic
-
dikinase
- nutrition
-
m-type
- medicine
-
spherocytosis
-
calprotectin
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The expected taxonomic range for this enzyme is: Archaea, Eukaryota, Bacteria
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EC NUMBER 
COMMENTARY 
2.7.1.40
-
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RECOMMENDED NAME
GeneOntology No.
pyruvate kinase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + pyruvate = ADP + phosphoenolpyruvate
UTP, GTP, CTP, ITP and dATP can also act as donors, also phosphorylates hydroxylamine and fluoride in the presence of CO2
-
-
-
ATP + pyruvate = ADP + phosphoenolpyruvate
catalyzes the addition of a proton and the loss of a phosphoryl group which is transferred to ADP
-
ATP + pyruvate = ADP + phosphoenolpyruvate
allosteric enzyme: homotropic
-
ATP + pyruvate = ADP + phosphoenolpyruvate
allosteric enzyme: homotropic
-
ATP + pyruvate = ADP + phosphoenolpyruvate
allosteric enzyme: homotropic
-
ATP + pyruvate = ADP + phosphoenolpyruvate
sigmoidal saturation curves with substrate and metal ions
-
ATP + pyruvate = ADP + phosphoenolpyruvate
model for allosteric regulation
Musa cavendishii
-
ATP + pyruvate = ADP + phosphoenolpyruvate
sigmoidal kinetics with respect to phosphoenolpyruvate
ATP + pyruvate = ADP + phosphoenolpyruvate
allosteric enzyme
ATP + pyruvate = ADP + phosphoenolpyruvate
compulsory-ordered tri-bi mechanism
-
ATP + pyruvate = ADP + phosphoenolpyruvate
modeling of the catalytic mechanism, overview
-
ATP + pyruvate = ADP + phosphoenolpyruvate
the kinetic mechanism is random order with a rapid equilibrium
ATP + pyruvate = ADP + phosphoenolpyruvate
allosteric enzyme: homotropic
-
-
ATP + pyruvate = ADP + phosphoenolpyruvate
allosteric enzyme: homotropic
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
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SYSTEMATIC NAME
IUBMB Comments
ATP:pyruvate 2-O-phosphotransferase
UTP, GTP, CTP, ITP and dATP can also act as donors. Also phosphorylates hydroxylamine and fluoride in the presence of CO2.
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CAS REGISTRY NUMBER
COMMENTARY
9001-59-6
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
wild-type strain WG 096 (yA2, paba A1) and transformant 9/402
-
-
Busycotypus canaliculatum
strain LT-2, highest activity in cells grown on glycolytic substrates, e.g. glucose, galactose, fructose or glycerol
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strain LT-2, highest activity in cells grown on glycolytic substrates, e.g. glucose, galactose, fructose or glycerol
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genes encoding pyruvate kinase and phosphofructokinase are cotranscribed and their expression is regulated at the transcriptional level in response to the sugars supplied
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641552, 641553, 660823, 672913, 673438, 673933, 674082, 674499, 676298, 691167, 692224, 692634, 692662, 707274, 707450, 707493, 707838, 707871, 707908, 708196, 708214, 708378, 708661, 708734, 708759, 709228, 709286, 709379, 709464, 709909, 710022, 710034, 710048, 710210, 710648, 721634, 721787, 721806, 721818, 721966, 723269, 723661, 737416, 737571, 738581, 739675, 739755
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-
-
-
-
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641520, 641561, 641572, 661628, 707515, 707516, 707517, 707643, 721683, 721688, 722155, 722396, 737796, 738760
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
significant evolutionary distance existing between the type I and type II isoenzymes in Gram-negative bacteria
evolution
-
significant evolutionary distance existing between the type I and type II isoenzymes in Gram-negative bacteria
-
malfunction
-
FcepsilonRI-mediated inhibition of M2-type PK is required for mast cell degranulation
malfunction
-
M2-PK inhibition rescues cells from glucose starvation-induced apoptotic cell death by increasing the metabolic activity
malfunction
-
the pyruvate kinase-deficient co-isogenic mouse strain CBAPk-1slc is protected against Babesia rodhaini infection
malfunction
-
pyruvate kinase-deficient Escherichia coli exhibits increased plasmid copy number and cyclic AMP levels
malfunction
-
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
-
pyruvate kinase deficiency provides protection against infection and replication of Plasmodium falciparum in human erythrocytes
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
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
-
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
-
consequence of PKM2 inhibition is a reduced glycolytic flux, which can be reflected by the rates of cellular glucose consumption and lactate production
malfunction
-
the absence of extracellular serine and glycine has a pronounced inhibitory effect on pyruvate kinase activity
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
-
hereditary enzyme deficiency leads to chronic nonspherocytic hemolytic anemia
malfunction
-
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
-
pyruvate kinase-deficient Escherichia coli exhibits increased plasmid copy number and cyclic AMP levels
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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
-
metabolism
-
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
-
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
-
pyruvate kinase is a crucial regulatory enzyme involved in glycolysis
metabolism
-
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
-
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
-
CDC19 or HTG2 is involved in the phenotype of high-temperature growth
metabolism
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pyruvate kinase catalyzes the final step in glycolysis converting phosphoenolpyruvate to pyruvate, it is a central metabolic regulator
metabolism
-
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
pyruvate kinase catalyzes the last but rate-limiting step of glycolysis
metabolism
-
red blood cell pyruvate kinase is a key regulatory enzyme of red cell metabolism
metabolism
-
pyruvate kinase isoenzyme M2 plays an important role in the control of glucose metabolism
metabolism
-
pyruvate kinase M2 activates mTORC1 by phosphorylating its inhibitor AKT1S1
metabolism
-
pyruvate kinase is a crucial regulatory enzyme involved in glycolysis
-
metabolism
-
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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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
-
M2-PK is a metabolic sensor which regulates cell proliferation, cell growth and apoptotic cell death in a glucose supply-dependent manner
physiological function
-
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
-
Oct-4-mediated transcriptional activity is positively regulated by PKM2
physiological function
-
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
-
vesicle-associated pyruvate kinase can support vesicular glutamate and other neurotransmitter uptake in the presence of its substrates
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
-
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
-
the enzyme is involved in the modified Embden-Meyerhof pathway
physiological function
-
PYK plays a central role in a number of proliferative and infectious diseases
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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required role of the active site in allosteric regulation involving substrate binding, requirement for monovalent and divalent cations, overview
physiological function
-
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
-
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
-
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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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
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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
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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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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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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
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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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
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 enzyme catalyzes the final step of glycolysis
physiological function
-
the enzyme is involved in glycogen catabolism
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
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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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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
-
the enzyme catalyzes the final step of glycolysis
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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
-
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
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
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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
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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
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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
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 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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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + AKT1S1
ADP + phospho-AKT1S1
-
the enzyme phosphorylates Ser202 and Ser203 of AKT1S1
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
the enzyme is involved in the modified Embden-Meyerhof pathway
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
allosteric enzyme
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
100% activity with ADP
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
4 phosphoenolpyruvate-binding sites/enzyme molecule
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
-
ADP + phosphoenolpyruvate
ATP + pyruvate
-
poor substrates: UDP, GDP
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
physiological role
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
Cardium tuberculatum
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
-
ADP + phosphoenolpyruvate
ATP + pyruvate
-
final regulatory point in catabolic Embden-Meyerhoff-Parnas pathway
-
-
-
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
probably involved in supplying additional carbon-skeletons for ammonium assimilation
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
-
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
ir
ADP + phosphoenolpyruvate
ATP + pyruvate
-
catalyzes the addition of a proton and the loss of a phosphoryl group which is transferred to ADP
-
-
ir
ADP + phosphoenolpyruvate
ATP + pyruvate
-
no positive cooperativity for ADP
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
-
673438, 674082, 674499, 676298, 707450, 707493, 707838, 707871, 707908, 708196, 708214, 708378, 708661, 708734, 708759, 709010, 709228, 709286, 709379, 709464, 709909, 710022, 710034, 710047, 710048, 710210, 710648
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
as a function of increasing pH (pH 6.5-8.0), PYK's affinity for phosphoenolpyruvate decreases, while affinity for ATP slightly increases
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
involved in regulation of metabolism of an aerobic organism capable of net glucose synthesis
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
-
ADP + phosphoenolpyruvate
ATP + pyruvate
-
-
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
Musa cavendishii
-
ADP preferred substrate, UDP, IDP, GDP and CDP may also be used with lower effectivity
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
-
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
100% activity with ADP
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
rate-controlling enzyme of glycolytic flux
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
the enzyme is expressed during the intraerythrocytic-stage of its developlental cycle that may play important metabolic roles during infection
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
important role of pyruvate kinase during malarial infection
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
other nucleoside diphosphates can replace ADP with a different rank order of effectiveness for enzyme form I and II
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
-
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
-
641555, 641563, 641564, 641572, 661404, 661406, 674052, 675943, 706831, 707914, 708372, 709817, 710084
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
the enzyme catalyzes an important regulatory step in the glycolysis pathway, the main route that provides energy for brain function
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
-
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
the enzyme is essential for multicellular development: fruiting body formation is abolished in mutant strain and indole-induced spore formation is delayed
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
-
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
ADP preferred substrate, UDP, IDP, GDP and CDP may also be used with lower effectivity
-
-
-
ADP + phosphoenolpyruvate
ATP + pyruvate
the substrate binding order of the Thermofilum pendens enzyme is independent despite lacking an internal positive charge
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
best nucleoside diphosphate substrate
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
positive cooperativity for phosphoenolpyruvate
-
-
?
ATP + prothymosin alpha
ADP + phospho-prothymosin alpha
-
isozyme M2-type acts as a ProTalpha kinase phosphorylating ProTalpha
-
-
?
ATP + prothymosin alpha
ADP + phospho-prothymosin alpha
-
in normal murine lymphocytes and in tumor cells M2-PK phosphorylates prothymosin alpha on a threonine
-
-
?
ATP + prothymosin alpha
ADP + phospho-prothymosin alpha
-
ProTalpha kinase activity
-
-
?
ATP + pyruvate
ADP + phosphoenolpyruvate
-
-
-
-
?
ATP + pyruvate
ADP + phosphoenolpyruvate
the enzyme catalyzes the final step of glycolysis
-
-
?
ATP + pyruvate
ADP + phosphoenolpyruvate
the enzyme catalyzes the final step of glycolysis
-
-
?
CDP + phosphoenolpyruvate
CTP + pyruvate
-
less effective than ADP
-
-
?
CDP + phosphoenolpyruvate
CTP + pyruvate
-
less effective than ADP
-
-
?
CDP + phosphoenolpyruvate
CTP + pyruvate
-
reaction at 25% the rate of ADP
-
-
?
CDP + phosphoenolpyruvate
CTP + pyruvate
-
poor substrate
-
-
?
CDP + phosphoenolpyruvate
CTP + pyruvate
-
less effective than ADP
-
-
?
CDP + phosphoenolpyruvate
CTP + pyruvate
-
less effective than ADP
-
-
?
CDP + phosphoenolpyruvate
CTP + pyruvate
-
reaction with PKp-isozyme at 30%, with PKc-isozyme at 12% the rate of ADP
-
-
?
CDP + phosphoenolpyruvate
CTP + pyruvate
-
less effective than ADP
-
-
?
CDP + phosphoenolpyruvate
CTP + pyruvate
-
less effective than ADP
-
-
?
CDP + phosphoenolpyruvate
CTP + pyruvate
-
less effective than ADP
-
-
?
CDP + phosphoenolpyruvate
CTP + pyruvate
-
less effective than ADP
-
-
?
dADP + phosphoenolpyruvate
dATP + pyruvate
-
23% activity compared to ADP
-
-
?
dADP + phosphoenolpyruvate
dATP + pyruvate
-
9.9% activity compared to ADP
-
-
?
dADP + phosphoenolpyruvate
dATP + pyruvate
-
26% activity compared to ADP
-
-
?
dCDP + phosphoenolpyruvate
dCTP + pyruvate
-
0.5% activity compared to ADP
-
-
?
dCDP + phosphoenolpyruvate
dCTP + pyruvate
-
0.082% activity compared to ADP
-
-
?
dCDP + phosphoenolpyruvate
dCTP + pyruvate
-
2.9% activity compared to ADP
-
-
?
dGDP + phosphoenolpyruvate
dGTP + pyruvate
-
10.2% activity compared to ADP
-
-
?
dGDP + phosphoenolpyruvate
dGTP + pyruvate
-
1.82% activity compared to ADP
-
-
?
dGDP + phosphoenolpyruvate
dGTP + pyruvate
-
44% activity compared to ADP
-
-
?
dTDP + phosphoenolpyruvate
dTTP + pyruvate
-
4.6% activity compared to ADP
-
-
?
dTDP + phosphoenolpyruvate
dTTP + pyruvate
-
0.035% activity compared to ADP
-
-
?
dTDP + phosphoenolpyruvate
dTTP + pyruvate
-
4.8% activity compared to ADP
-
-
?
GDP + phosphoenolpyruvate
GTP + pyruvate
Cardium tuberculatum
-
less effective than ADP
-
-
?
GDP + phosphoenolpyruvate
GTP + pyruvate
-
less effective than ADP
-
-
?
GDP + phosphoenolpyruvate
GTP + pyruvate
-
reaction at 55% the rate of ADP
-
-
?
GDP + phosphoenolpyruvate
GTP + pyruvate
-
less effective than ADP
-
-
?
GDP + phosphoenolpyruvate
GTP + pyruvate
-
less effective than ADP
-
-
?
GDP + phosphoenolpyruvate
GTP + pyruvate
-
less effective than ADP
-
-
?
GDP + phosphoenolpyruvate
GTP + pyruvate
-
reaction for PKc-isozyme at 71%, for PKp-isozyme at 39% the rate of ADP
-
-
?
GDP + phosphoenolpyruvate
GTP + pyruvate
-
less effective than ADP
-
-
?
GDP + phosphoenolpyruvate
GTP + pyruvate
-
less effective than ADP
-
-
?
IDP + phosphoenolpyruvate
ITP + pyruvate
-
less effective than ADP
-
-
?
IDP + phosphoenolpyruvate
ITP + pyruvate
Cardium tuberculatum
-
less effective than ADP
-
-
?
IDP + phosphoenolpyruvate
ITP + pyruvate
-
less effective than ADP
-
-
?
IDP + phosphoenolpyruvate
ITP + pyruvate
-
reaction at 53% the rate of ADP
-
-
?
IDP + phosphoenolpyruvate
ITP + pyruvate
-
less effective than ADP
-
-
?
IDP + phosphoenolpyruvate
ITP + pyruvate
-
less effective than ADP
-
-
?
IDP + phosphoenolpyruvate
ITP + pyruvate
-
reaction with PKp-isozyme at 20%, with PKc-isozyme at 89% the rate of ADP
-
-
?
IDP + phosphoenolpyruvate
ITP + pyruvate
-
less effective than ADP
-
-
?
UDP + phosphoenolpyruvate
UTP + pyruvate
-
less effective than ADP
-
-
?
UDP + phosphoenolpyruvate
UTP + pyruvate
-
less effective than ADP
-
-
?
UDP + phosphoenolpyruvate
UTP + pyruvate
-
less effective than ADP
-
-
?
UDP + phosphoenolpyruvate
UTP + pyruvate
-
reaction at about 70% the rate of ADP, PKc-isozyme
-
-
?
UDP + phosphoenolpyruvate
UTP + pyruvate
-
less effective than ADP
-
-
?
UDP + phosphoenolpyruvate
UTP + pyruvate
-
reaction at about 31% the rate of ADP, PKp-isozyme
-
-
?
UDP + phosphoenolpyruvate
UTP + pyruvate
-
less effective than ADP
-
-
?
UDP + phosphoenolpyruvate
UTP + pyruvate
-
less effective than ADP
-
-
?
additional information
?
-
-
broad specificity for nucleoside diphosphates
-
-
-
additional information
?
-
-
allosteric enzyme: homotropic
-
-
-
additional information
?
-
-
pyruvate kinase M2 is a phosphotyrosine-binding protein
-
-
-
additional information
?
-
-
the SUMO-E3 ligase protein PIAS3 (inhibitor of activated STAT3) physically interacts with M2-PK and its isoenzyme M1-PK
-
-
-
additional information
?
-
mitogenic factor LPA, SUMO-E3 ligase, tumor endothelial marker-8, hepatitis C virus-NS5B RNA polymerase and HERC-1 via its HECT domain bind to isozyme PKM2
-
-
-
additional information
?
-
-
nuclear M2-PK participates in the phosphorylation of the epsilon-amino group of histone 1 by direct phosphate transfer from PEP without requiring ATP. M2-PK directly inters with different oncoproteins and components of the protein kinase cascade, such as HPV-16 E7, the tyrosine kinases pp60v-src, BCR-ABL, ETV6-NTRK3, FGFR-1, FLT3 and JAK-2, the serine/threonine kinase A-Raf, cytoplasmic promyelocytic leukemia tumor suppressor protein as well as phosphotyrosine peptides
-
-
-
additional information
?
-
-
allosteric enzyme: homotropic
-
-
-
additional information
?
-
-
the recombinant enzyme shows the following range in its substrate specificity: ADP>dADP>dGDP>dCDP>TDP
-
-
-
additional information
?
-
-
pyruvate kinase is a substrate of protein kinase A
-
-
-
additional information
?
-
-
pyruvate kinase is a substrate of protein kinase A
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + AKT1S1
ADP + phospho-AKT1S1
-
the enzyme phosphorylates Ser202 and Ser203 of AKT1S1
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
the enzyme is involved in the modified Embden-Meyerhof pathway
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
allosteric enzyme
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
physiological role
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
final regulatory point in catabolic Embden-Meyerhoff-Parnas pathway
-
-
-
ADP + phosphoenolpyruvate
ATP + pyruvate
-
probably involved in supplying additional carbon-skeletons for ammonium assimilation
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
-
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
involved in regulation of metabolism of an aerobic organism capable of net glucose synthesis
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
rate-controlling enzyme of glycolytic flux
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
the enzyme is expressed during the intraerythrocytic-stage of its developlental cycle that may play important metabolic roles during infection
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
-
the enzyme catalyzes an important regulatory step in the glycolysis pathway, the main route that provides energy for brain function
-
-
?
ADP + phosphoenolpyruvate
ATP + pyruvate
Q8GQS6
the enzyme is essential for multicellular development: fruiting body formation is abolished in mutant strain and indole-induced spore formation is delayed
-
-
?
ATP + prothymosin alpha
ADP + phospho-prothymosin alpha
-
in normal murine lymphocytes and in tumor cells M2-PK phosphorylates prothymosin alpha on a threonine
-
-
?
ATP + pyruvate
ADP + phosphoenolpyruvate
-
-
-
-
?
ATP + pyruvate
ADP + phosphoenolpyruvate
Q8ZYE0
the enzyme catalyzes the final step of glycolysis
-
-
?
ATP + pyruvate
ADP + phosphoenolpyruvate
Q8ZYE0
the enzyme catalyzes the final step of glycolysis
-
-
?
additional information
?
-
P14618
mitogenic factor LPA, SUMO-E3 ligase, tumor endothelial marker-8, hepatitis C virus-NS5B RNA polymerase and HERC-1 via its HECT domain bind to isozyme PKM2
-
-
-
additional information
?
-
-
nuclear M2-PK participates in the phosphorylation of the epsilon-amino group of histone 1 by direct phosphate transfer from PEP without requiring ATP. M2-PK directly inters with different oncoproteins and components of the protein kinase cascade, such as HPV-16 E7, the tyrosine kinases pp60v-src, BCR-ABL, ETV6-NTRK3, FGFR-1, FLT3 and JAK-2, the serine/threonine kinase A-Raf, cytoplasmic promyelocytic leukemia tumor suppressor protein as well as phosphotyrosine peptides
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ADP
-
-
673438, 674082, 674499, 676298, 707274, 707450, 707493, 707838, 707871, 707908, 708196, 708214, 708378, 708661, 708734, 708759, 709010, 709228, 709286, 709379, 709464, 709909, 710022, 710034, 710047, 710048, 710210, 710648, 721787
ADP
-
-
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Cd2+
-
multiphasical activation, at pH below physiological value, inhibits at physiological pH
Co2+
Cu2+
-
divalent cation required, at 1 mM Cu2+ activation results in 86% of the activity with Mg2+
divalent cation
Fe2+
-
the enzyme is dependent on Mn2+ ion for its activity. Fe2+ and Mg2+ show 70 and 20% of the Mn2+ activity, respectively. No activity is detected without metal or with Zn2+, Cu2+, Co2+, and Ni2+
K+
Mg2+
Mn2+
Monovalent cation
Na+
NH4+
Ni2+
-
divalent cation required, at 1 mM Ni2+ activation results in 2% of the activity with Mg2+
sulfate
each monomer in the asymmetric unit of CpPyK binds two sulfate ions at equivalent positions, one in the C-domain and the other at the interface of the A and C domains, binding structure, overview. The sulfate ion in the C-domain occupies a position corresponding to the 6-phosphate of the effector molecule in different PyKs
Tl+
-
wild-type enzyme and the three mutant enzymes T298S, T298C and T298A show no measurable activity in the presence of K+ or Tl+. Tl+ can activate wild-type enzyme to 85% the activity in the presence of K+. With T298S, T298, and T298A, Tl+ is 1.2-1.8fold better activator than is K+ based on the measured turnover number values
Zn2+
additional information
Ca2+
-
divalent cation required, at 1 mM Ca2+ activation results in 14% of the activity with Mg2+
Ca2+
-
divalent cation required, at 1 mM Ca2+ activation results in 7% of the activity with Mg2+
Ca2+
-
divalent cation required, at 1 mM Ca2+ activation results in 3% of the activity with Mg2+
Co2+
-
divalent cation required, at 1 mM Co2+ activation results in 170% of the activity with Mg2+
Co2+
-
divalent cation required, at 1 mM Co2+ activation results in 80% of the activity with Mn2+
Co2+
-
multiphasical activation, at pH below physiological value, inhibits at physiological pH
Co2+
-
divalent cation required, at 1 mM Co2+ activation results in 120% of the activity with Mg2+
divalent cation
-
requirement; requires both a divalent and a monovalent cation
divalent cation
-
requirement; requires both a divalent and a monovalent cation
divalent cation
-
requirement; requires both a divalent and a monovalent cation
K+
-
apparent Km-value: 0.48 mM; only together with activating divalent cation
K+
-
best activator at optimal conditions, in decreasing order of efficiency: K+, Rb+, Cs+, Na+, NH4+, Li+; requirement
K+
-
essential activator, in the presence of K+ the affinities for phosphoenolpyruvate, ADP, ADP-Cr2+, and oxalate are 2-6fold higher than in the absence of K+ when ADP cannot bind to the enzyme until phosphoenolpyruvate forms a competent active site
K+
-
in aqueous media, muscle pyruvate kinase is highly selective for K+ over Na+. Dimethylsulfoxide favors the partition of K+ and Na+ into the monovalent and divalent cation binding sites of the enzyme. The kinetics of the enzyme at subsaturating concentrations of activators show that K+ and Mg2+ exhibit high selectivity for their respective cation binding sites, whereas when Na+ substitutes K+, Na+ and Mg2+ bind with high affinity to their incorrect sites. The ratio of the affnities of Mg2+ and K+ for the monovalent cation binding site is close to 200. For Na+ and Mg2+ this ratio is approximately 20. The data suggest that K+ induces conformational changes that prevent the binding of Mg2+ to the monovalent cation binding site