Phosphofructokinase 1

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6-phosphofructokinase
Phosphofructokinase 6PFK wpmp.png
Identifiers
EC no. 2.7.1.11
CAS no. 9001-80-3
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BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
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NCBI proteins
Phosphofructokinase
Identifiers
SymbolPFK
Pfam PF00365
Pfam clan CL0240
InterPro IPR000023
PROSITE PDOC00336
SCOP2 5pfk / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1kzh ​, 1mto ​, 1pfk ​, 1zxx ​, 2f48 ​, 2pfk ​, 3pfk ​, 4pfk ​, 6pfk ​

Phosphofructokinase-1 (PFK-1) is one of the most important regulatory enzymes (EC 2.7.1.11) of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors. PFK-1 catalyzes the important "committed" step of glycolysis, the conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP. Glycolysis is the foundation for respiration, both anaerobic and aerobic. Because phosphofructokinase (PFK) catalyzes the ATP-dependent phosphorylation to convert fructose-6-phosphate into fructose 1,6-bisphosphate and ADP, it is one of the key regulatory steps of glycolysis. [1] PFK is able to regulate glycolysis through allosteric inhibition, and in this way, the cell can increase or decrease the rate of glycolysis in response to the cell's energy requirements. For example, a high ratio of ATP to ADP will inhibit PFK and glycolysis. The key difference between the regulation of PFK in eukaryotes and prokaryotes is that in eukaryotes PFK is activated by fructose 2,6-bisphosphate. The purpose of fructose 2,6-bisphosphate is to supersede ATP inhibition, thus allowing eukaryotes to have greater sensitivity to regulation by hormones like glucagon and insulin. [2]

Contents

β-D-fructose 6-phosphate Phosphofructokinase 1β-D-fructose 1,6-bisphosphate
Beta-D-fructose-6-phosphate wpmp.png   Beta-D-fructose-1,6-bisphosphate wpmp.png
ATP ADP
Biochem reaction arrow reversible YYYY horiz med.svg
PiH2O
 
  Fructose bisphosphatase

Structure

Mammalian PFK1 is a 340kd [3] tetramer composed of different combinations of three types of subunits: muscle (M), liver (L), and platelet (P). The composition of the PFK1 tetramer differs according to the tissue type it is present in. For example, mature muscle expresses only the M isozyme, therefore, the muscle PFK1 is composed solely of homotetramers of M4. The liver and kidneys express predominantly the L isoform. In erythrocytes, both M and L subunits randomly tetramerize to form M4, L4 and the three hybrid forms of the enzyme (ML3, M2L2, M3L). As a result, the kinetic and regulatory properties of the various isoenzymes pools are dependent on subunit composition. Tissue-specific changes in PFK activity and isoenzymic content contribute significantly to the diversities of glycolytic and gluconeogenic rates which have been observed for different tissues. [4]

PFK1 is an allosteric enzyme and has a structure similar to that of hemoglobin in so far as it is a dimer of a dimer. [5] One half of each dimer contains the ATP binding site whereas the other half the substrate (fructose-6-phosphate or (F6P)) binding site as well as a separate allosteric binding site. [6]

Each subunit of the tetramer is 319 amino acids and consists of two domains: one that binds the substrate ATP, and the other that binds fructose-6-phosphate. Each domain is a beta barrel, and has a cylindrical beta sheet surrounded by alpha helices.

On the opposite side of the each subunit from each active site is the allosteric site, at the interface between subunits in the dimer. ATP and AMP compete for this site. The N-terminal domain has a catalytic role binding the ATP, and the C-terminal has a regulatory role [7]

Mechanism

PFK1 is an allosteric enzyme whose activity can be described using the symmetry model of allosterism [8] whereby there is a concerted transition from an enzymatically inactive T-state to the active R-state. F6P binds with a high affinity to the R state but not the T state enzyme. For every molecule of F6P that binds to PFK1, the enzyme progressively shifts from T state to the R state. Thus a graph plotting PFK1 activity against increasing F6P concentrations would adopt the sigmoidal curve shape traditionally associated with allosteric enzymes.

PFK1 belongs to the family of phosphotransferases and it catalyzes the transfer of γ-phosphate from ATP to fructose-6-phosphate. The PFK1 active site comprises both the ATP-Mg2+ and the F6P binding sites. Some proposed residues involved with substrate binding in E. coli PFK1 include Asp127 and Arg171. [9] In B. stearothermophilus PFK1, the positively charged side chain of Arg162 residue forms a hydrogen-bonded salt bridge with the negatively charged phosphate group of F6P, an interaction which stabilizes the R state relative to the T state and is partly responsible for the homotropic effect of F6P binding. In the T state, enzyme conformation shifts slightly such that the space previously taken up by the Arg162 is replaced with Glu161. This swap in positions between adjacent amino acid residues inhibits the ability of F6P to bind the enzyme.

Allosteric activators such as AMP and ADP bind to the allosteric site as to facilitate the formation of the R state by inducing structural changes in the enzyme. Similarly, inhibitors such as ATP and PEP bind to the same allosteric site and facilitate the formation of the T state, thereby inhibiting enzyme activity.

The hydroxyl oxygen of carbon 1 does a nucleophilic attack on the beta phosphate of ATP. These electrons are pushed to the anhydride oxygen between the beta and gamma phosphates of ATP. [10] [11]

Mechanism of phosphofructokinase 1 AbhinavBiochemMechanism.JPG
Mechanism of phosphofructokinase 1

Regulation

PFK1 is the most important control site in the mammalian glycolytic pathway. This step is subject to extensive regulation since it is not only highly exergonic under physiological conditions, but also because it is a committed step – the first irreversible reaction unique to the glycolytic pathway. This leads to a precise control of glucose and the other monosaccharides galactose and fructose going down the glycolytic pathway. Before this enzyme's reaction, glucose-6-phosphate can potentially travel down the pentose phosphate pathway, or be converted to glucose-1-phosphate for glycogenesis.

PFK1 is allosterically inhibited by high levels of ATP but AMP reverses the inhibitory action of ATP. Therefore, the activity of the enzyme increases when the cellular ATP/AMP ratio is lowered. Glycolysis is thus stimulated when energy charge falls. PFK1 has two sites with different affinities for ATP which is both a substrate and an inhibitor. [3]

PFK1 is also inhibited by low pH levels which augment the inhibitory effect of ATP. The pH falls when muscle is functioning anaerobically and producing excessive quantities of lactic acid (although lactic acid is not itself the cause of the decrease in pH [12] ). This inhibitory effect serves to protect the muscle from damage that would result from the accumulation of too much acid. [3]

Finally, PFK1 is allosterically inhibited by PEP, citrate, and ATP. Phosphoenolpyruvic acid is a product further downstream the glycolytic pathway. Although citrate does build up when the Krebs Cycle enzymes approach their maximum velocity, it is questionable whether citrate accumulates to a sufficient concentration to inhibit PFK-1 under normal physiological conditions[ citation needed ]. ATP concentration build up indicates an excess of energy and does have an allosteric modulation site on PFK1 where it decreases the affinity of PFK1 for its substrate.

PFK1 is allosterically activated by a high concentration of AMP, but the most potent activator is fructose 2,6-bisphosphate, which is also produced from fructose-6-phosphate by PFK2. Hence, an abundance of F6P results in a higher concentration of fructose 2,6-bisphosphate (F-2,6-BP). The binding of F-2,6-BP increases the affinity of PFK1 for F6P and diminishes the inhibitory effect of ATP. This is an example of feedforward stimulation as glycolysis is accelerated when glucose is abundant. [3]

PFK activity is reduced through repression of synthesis by glucagon. Glucagon activates protein kinase A which, in turn, shuts off the kinase activity of PFK2. This reverses any synthesis of F-2,6-BP from F6P and thus de-activates PFK1.

The precise regulation of PFK1 prevents glycolysis and gluconeogenesis from occurring simultaneously. However, there is substrate cycling between F6P and F-1,6-BP. Fructose-1,6-bisphosphatase (FBPase) catalyzes the hydrolysis of F-1,6-BP back to F6P, the reverse reaction catalyzed by PFK1. There is a small amount of FBPase activity during glycolysis and some PFK1 activity during gluconeogenesis. This cycle allows for the amplification of metabolic signals as well as the generation of heat by ATP hydrolysis.

Serotonin (5-HT) increases PFK by binding to the 5-HT(2A) receptor, causing the tyrosine residue of PFK to be phosphorylated via phospholipase C. This in turn redistributes PFK within the skeletal muscle cells. Because PFK regulates glycolytic flux, serotonin plays a regulatory role in glycolysis [13]

Genes

There are three phosphofructokinase genes in humans:

Clinical significance

A genetic mutation in the PFKM gene results in Tarui's disease, which is a glycogen storage disease where the ability of certain cell types to utilize carbohydrates as a source of energy is impaired. [14]

Tarui disease is a glycogen storage disease with symptoms including muscle weakness (myopathy) and exercise induced cramping and spasms, myoglobinuria (presence of myoglobin in urine, indicating muscle destruction) and compensated hemolysis. ATP is a natural allosteric inhibitor of PFK, in order to prevent unnecessary production of ATP through glycolysis. However, a mutation in Asp(543)Ala can result in ATP having a stronger inhibitory effect (due to increased binding to PFK's inhibitory allosteric binding site). [15] [16]

Phosphofructokinase mutation and cancer: In order for cancer cells to meet their energy requirements due to their rapid cell growth and division, they survive more effectively when they have a hyperactive phosphofructokinase 1 enzyme. [17] [18] When cancer cells grow and divide quickly, they initially do not have as much blood supply, and can thus have hypoxia (oxygen deprivation), and this triggers O-GlcNAcylation at serine 529 of PFK. This modification inhibits PFK1 activity and supports cancer proliferation, in contrast with the view that high PFK1 activity is necessary for cancer. This may be due to redirecting glucose flux towards the pentose phosphate pathway to generate NADPH to detoxify reactive oxygen species. [19]

Herpes simplex type 1 and phosphofructokinase: Some viruses, including HIV, HCMV and Mayaro affect cellular metabolic pathways such as glycolysis by a MOI-dependent increase in the activity of PFK. The mechanism that Herpes increases PFK activity is by phosphorylating the enzyme at the serine residues. The HSV-1 induced glycolysis increases ATP content, which is critical for the virus's replication. [20]

See also

Related Research Articles

<span class="mw-page-title-main">Glycolysis</span> Series of interconnected biochemical reactions

Glycolysis is the metabolic pathway that converts glucose into pyruvate and, in most organisms, occurs in the liquid part of cells. The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH). Glycolysis is a sequence of ten reactions catalyzed by enzymes.

<span class="mw-page-title-main">Allosteric regulation</span> Regulation of enzyme activity

In the fields of biochemistry and pharmacology an allosteric regulator is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the protein's activity, either enhancing or inhibiting its function. In contrast, substances that bind directly to an enzyme's active site or the binding site of the endogenous ligand of a receptor are called orthosteric regulators or modulators.

<span class="mw-page-title-main">Fructose 1,6-bisphosphatase</span> Class of enzymes

The enzyme fructose bisphosphatase (EC 3.1.3.11; systematic name D-fructose-1,6-bisphosphate 1-phosphohydrolase) catalyses the conversion of fructose-1,6-bisphosphate to fructose 6-phosphate in gluconeogenesis and the Calvin cycle, which are both anabolic pathways:

<span class="mw-page-title-main">Tumor hypoxia</span> Situation where tumor cells have been deprived of oxygen

Tumor hypoxia is the situation where tumor cells have been deprived of oxygen. As a tumor grows, it rapidly outgrows its blood supply, leaving portions of the tumor with regions where the oxygen concentration is significantly lower than in healthy tissues. Hypoxic microenvironments in solid tumors are a result of available oxygen being consumed within 70 to 150 μm of tumor vasculature by rapidly proliferating tumor cells thus limiting the amount of oxygen available to diffuse further into the tumor tissue. In order to support continuous growth and proliferation in challenging hypoxic environments, cancer cells are found to alter their metabolism. Furthermore, hypoxia is known to change cell behavior and is associated with extracellular matrix remodeling and increased migratory and metastatic behavior.

<span class="mw-page-title-main">PFP (enzyme)</span> Class of enzymes

Diphosphate—fructose-6-phosphate 1-phosphotransferase also known as PFP is an enzyme of carbohydrate metabolism in plants and some bacteria. The enzyme catalyses the reversible interconversion of fructose 6-phosphate and fructose 1,6-bisphosphate using inorganic pyrophosphate as the phosphoryl donor:

<span class="mw-page-title-main">Pyruvate kinase</span> Class of enzymes

Pyruvate kinase is the enzyme involved in the last step of glycolysis. It catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to adenosine diphosphate (ADP), yielding one molecule of pyruvate and one molecule of ATP. Pyruvate kinase was inappropriately named before it was recognized that it did not directly catalyze phosphorylation of pyruvate, which does not occur under physiological conditions. Pyruvate kinase is present in four distinct, tissue-specific isozymes in animals, each consisting of particular kinetic properties necessary to accommodate the variations in metabolic requirements of diverse tissues.

<span class="mw-page-title-main">Phosphofructokinase 2</span> Class of enzymes

Phosphofructokinase-2 (6-phosphofructo-2-kinase, PFK-2) or fructose bisphosphatase-2 (FBPase-2), is an enzyme indirectly responsible for regulating the rates of glycolysis and gluconeogenesis in cells. It catalyzes formation and degradation of a significant allosteric regulator, fructose-2,6-bisphosphate (Fru-2,6-P2) from substrate fructose-6-phosphate. Fru-2,6-P2 contributes to the rate-determining step of glycolysis as it activates enzyme phosphofructokinase 1 in the glycolysis pathway, and inhibits fructose-1,6-bisphosphatase 1 in gluconeogenesis. Since Fru-2,6-P2 differentially regulates glycolysis and gluconeogenesis, it can act as a key signal to switch between the opposing pathways. Because PFK-2 produces Fru-2,6-P2 in response to hormonal signaling, metabolism can be more sensitively and efficiently controlled to align with the organism's glycolytic needs. This enzyme participates in fructose and mannose metabolism. The enzyme is important in the regulation of hepatic carbohydrate metabolism and is found in greatest quantities in the liver, kidney and heart. In mammals, several genes often encode different isoforms, each of which differs in its tissue distribution and enzymatic activity. The family described here bears a resemblance to the ATP-driven phospho-fructokinases; however, they share little sequence similarity, although a few residues seem key to their interaction with fructose 6-phosphate.

<span class="mw-page-title-main">Fructose 1,6-bisphosphate</span> Chemical compound

Fructose 1,6-bisphosphate, known in older publications as Harden-Young ester, is fructose sugar phosphorylated on carbons 1 and 6. The β-D-form of this compound is common in cells. Upon entering the cell, most glucose and fructose is converted to fructose 1,6-bisphosphate.

A futile cycle, also known as a substrate cycle, occurs when two metabolic pathways run simultaneously in opposite directions and have no overall effect other than to dissipate energy in the form of heat. The reason this cycle was called "futile" cycle was because it appeared that this cycle operated with no net utility for the organism. As such, it was thought of being a quirk of the metabolism and thus named a futile cycle. After further investigation it was seen that futile cycles are very important for regulating the concentrations of metabolites. For example, if glycolysis and gluconeogenesis were to be active at the same time, glucose would be converted to pyruvate by glycolysis and then converted back to glucose by gluconeogenesis, with an overall consumption of ATP. Futile cycles may have a role in metabolic regulation, where a futile cycle would be a system oscillating between two states and very sensitive to small changes in the activity of any of the enzymes involved. The cycle does generate heat, and may be used to maintain thermal homeostasis, for example in the brown adipose tissue of young mammals, or to generate heat rapidly, for example in insect flight muscles and in hibernating animals during periodical arousal from torpor. It has been reported that the glucose metabolism substrate cycle is not a futile cycle but a regulatory process. For example, when energy is suddenly needed, ATP is replaced by AMP, a much more reactive adenine.

<span class="mw-page-title-main">Fructose 2,6-bisphosphate</span> Chemical compound

Fructose 2,6-bisphosphate, abbreviated Fru-2,6-P2, is a metabolite that allosterically affects the activity of the enzymes phosphofructokinase 1 (PFK-1) and fructose 1,6-bisphosphatase (FBPase-1) to regulate glycolysis and gluconeogenesis. Fru-2,6-P2 itself is synthesized and broken down in either direction by the integrated bifunctional enzyme phosphofructokinase 2 (PFK-2/FBPase-2), which also contains a phosphatase domain and is also known as fructose-2,6-bisphosphatase. Whether the kinase and phosphatase domains of PFK-2/FBPase-2 are active or inactive depends on the phosphorylation state of the enzyme.

<span class="mw-page-title-main">Phosphofructokinase</span> Enzyme in glycolysis

Phosphofructokinase (PFK) is a kinase enzyme that phosphorylates fructose 6-phosphate in glycolysis.

Glucose-1,6-bisphosphate synthase is a type of enzyme called a phosphotransferase and is involved in mammalian starch and sucrose metabolism. It catalyzes the transfer of a phosphate group from 1,3-bisphosphoglycerate to glucose-1-phosphate, yielding 3-phosphoglycerate and glucose-1,6-bisphosphate.

<span class="mw-page-title-main">Enzyme activator</span> Molecules which increase enzyme activity

Enzyme activators are molecules that bind to enzymes and increase their activity. They are the opposite of enzyme inhibitors. These molecules are often involved in the allosteric regulation of enzymes in the control of metabolism. An example of an enzyme activator working in this way is fructose 2,6-bisphosphate, which activates phosphofructokinase 1 and increases the rate of glycolysis in response to the hormone glucagon. In some cases, when a substrate binds to one catalytic subunit of an enzyme, this can trigger an increase in the substrate affinity as well as catalytic activity in the enzyme's other subunits, and thus the substrate acts as an activator.

<span class="mw-page-title-main">PFKM</span> Mammalian protein found in Homo sapiens

6-phosphofructokinase, muscle type is an enzyme that in humans is encoded by the PFKM gene on chromosome 12. Three phosphofructokinase isozymes exist in humans: muscle, liver and platelet. These isozymes function as subunits of the mammalian tetramer phosphofructokinase, which catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate. Tetramer composition varies depending on tissue type. This gene encodes the muscle-type isozyme. Mutations in this gene have been associated with glycogen storage disease type VII, also known as Tarui disease. Alternatively spliced transcript variants have been described.[provided by RefSeq, Nov 2009]

<span class="mw-page-title-main">PFKFB3</span> Protein-coding gene in the species Homo sapiens

PFKFB3 is a gene that encodes the 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 enzyme in humans. It is one of 4 tissue-specific PFKFB isoenzymes identified currently (PFKFB1-4).

<span class="mw-page-title-main">PFKL</span> Mammalian protein found in Homo sapiens

6-phosphofructokinase, liver type (PFKL) is an enzyme that in humans is encoded by the PFKL gene on chromosome 21. This gene encodes the liver (L) isoform of phosphofructokinase-1, an enzyme that catalyzes the conversion of D-fructose 6-phosphate to D-fructose 1,6-bisphosphate, which is a key step in glucose metabolism (glycolysis). This enzyme is a tetramer that may be composed of different subunits encoded by distinct genes in different tissues. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

<span class="mw-page-title-main">PFKP</span> Mammalian protein found in Homo sapiens

Phosphofructokinase, platelet, also known as PFKP is an enzyme which in humans is encoded by the PFKP gene.

<span class="mw-page-title-main">PFKFB2</span> Protein-coding gene in the species Homo sapiens

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 is an enzyme that in humans is encoded by the PFKFB2 gene.

Bisphosphate may refer to:

<span class="mw-page-title-main">TP53-inducible glycolysis and apoptosis regulator</span> Protein-coding gene in the species Homo sapiens

The TP53-inducible glycolysis and apoptosis regulator (TIGAR) also known as fructose-2,6-bisphosphatase TIGAR is an enzyme that in humans is encoded by the C12orf5 gene.

References

  1. ↑ Walker, L.R.; Simcock, D.C.; Pedley, K.C.; Simpson, H.V.; Brown, S. (April 2012). "The kinetics and regulation of phosphofructokinase from Teladorsagia circumcincta". Experimental Parasitology. 130 (4): 348–353. doi:10.1016/j.exppara.2012.02.011. ISSN   0014-4894. PMID   22402411.
  2. ↑ Usenik A, Legiša M (Nov 2010). Kobe B (ed.). "Evolution of allosteric citrate binding sites on 6-phosphofructo-1-kinase". PLOS ONE. 5 (11): 677–683. Bibcode:2010PLoSO...515447U. doi: 10.1371/journal.pone.0015447 . PMC   2990764 . PMID   21124851.
  3. 1 2 3 4 Stryer L, Berg JM, Tymoczko JL (2007). Biochemistry (Sixth ed.). San Francisco: W.H. Freeman. ISBN   978-0-7167-8724-2.
  4. ↑ Dunaway GA, Kasten TP, Sebo T, Trapp R (May 1988). "Analysis of the phosphofructokinase subunits and isoenzymes in human tissues". Biochem. J. 251 (3): 677–83. doi:10.1042/bj2510677. PMC   1149058 . PMID   2970843.
  5. ↑ PDB: 4pfk ​; Evans PR, Farrants GW, Hudson PJ (June 1981). "Phosphofructokinase: structure and control". Philosophical Transactions of the Royal Society B. 293 (1063): 53–62. Bibcode:1981RSPTB.293...53E. doi: 10.1098/rstb.1981.0059 . PMID   6115424.
  6. ↑ Shirakihara Y, Evans PR (December 1988). "Crystal structure of the complex of phosphofructokinase from Escherichia coli with its reaction products". J. Mol. Biol. 204 (4): 973–94. doi:10.1016/0022-2836(88)90056-3. PMID   2975709.
  7. ↑ Banaszak K, Mechin I, Obmolova G, Oldham M, Chang SH, Ruiz T, Radermacher M, Kopperschläger G, Rypniewski W (March 2011). "The crystal structures of eukaryotic phosphofructokinases from baker's yeast and rabbit skeletal muscle". J Mol Biol. 407 (7): 284–97. doi:10.1016/j.jmb.2011.01.019. PMID   21241708.
  8. ↑ Peskov K, Goryanin I, Demin O (August 2008). "Kinetic model of phosphofructokinase-1 from Escherichia coli". J Bioinform Comput Biol. 6 (4): 843–67. doi:10.1142/S0219720008003643. PMID   18763746.
  9. ↑ Hellinga HW, Evans PR (1987). "Mutations in the active site of Escherichia coli phosphofructokinase". Nature. 327 (6121): 437–9. doi:10.1038/327437a0. PMID   2953977. S2CID   4357039.
  10. ↑ Phong WY, Lin W, Rao SP, Dick T, Alonso S, Pethe K (Aug 2013). Parish T (ed.). "Characterization of Phosphofructokinase Activity in Mycobacterium tuberculosis Reveals That a Functional Glycolytic Carbon Flow Is Necessary to Limit the Accumulation of Toxic Metabolic Intermediates under Hypoxia". PLOS ONE. 8 (2): 1198–206. Bibcode:2013PLoSO...856037P. doi: 10.1371/journal.pone.0056037 . PMC   3567006 . PMID   23409118.
  11. ↑ Papagianni M, Avramidis N (May 2012). "Engineering the central pathways in Lactococcus lactis: functional expression of the phosphofructokinase (pfk) and alternative oxidase (aox1) genes from Aspergillus niger in Lactococcus lactis facilitates improved carbon conversion rates under oxidizing conditions". Enzyme and Microbial Technology. 51 (113): 125–30. doi:10.1016/j.enzmictec.2012.04.007. PMID   22759530.
  12. ↑ Lindinger, Michael I.; Kowalchuk, John M.; Heigenhauser, George J. F. (2005-09-01). "Applying physicochemical principles to skeletal muscle acid-base status". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 289 (3): R891–R894. doi:10.1152/ajpregu.00225.2005. ISSN   0363-6119. PMID   16105823.
  13. ↑ Coelho WS, Sola-Penna M (Jan 2013). "Serotonin regulates 6-phosphofructo-1-kinase activity in a PLC-PKC-CaMK II- and Janus kinase-dependent signaling pathway". Mol. Cell. Biochem. 372 (1–2): 211–20. doi:10.1007/s11010-012-1462-0. PMID   23010892. S2CID   14570273.
  14. ↑ Nakajima H, Raben N, Hamaguchi T, Yamasaki T (March 2002). "Phosphofructokinase deficiency; past, present and future". Curr. Mol. Med. 2 (2): 197–212. doi:10.2174/1566524024605734. PMID   11949936.
  15. ↑ Bruser A, KirchbergerJ, Schoneberg T (Oct 2012). "Altered allosteric regulation of muscle 6-phosphofructokinase causes Tarui disease". Biochem Biophys Res Commun. 427 (1): 133–7. doi:10.1016/j.bbrc.2012.09.024. PMID   22995305.
  16. ↑ Brüser A, Kirchberger J, Schöneberg T (October 2012). "Altered allosteric regulation of muscle 6-phosphofructokinase causes Tarui disease". Biochem. Biophys. Res. Commun. 427 (1): 133–7. doi:10.1016/j.bbrc.2012.09.024. PMID   22995305.
  17. ↑ Gomez LS, Zancan P, Marcondes MC, Ramos-Santos L, Meyer-Fernandes JR, Sola-Penna M, Da Silva D (Feb 2013). "Resveratrol decreases breast cancer cell viability and glucose metabolism by inhibiting 6-phosphofructo-1-kinase". Biochimie. 95 (6): 1336–43. doi: 10.1016/j.biochi.2013.02.013 . PMID   23454376.
  18. ↑ Vaz CV, Alves MG, Marques R, Moreira PI, Oliveira PF, Maia CJ, Socorro S (Feb 2013). "Androgen-responsive and nonresponsive prostate cancer cells present a distinct glycolytic metabolism profile". Int J Biochem Cell Biol. 44 (11): 2077–84. doi:10.1016/j.biocel.2012.08.013. PMID   22964025.
  19. ↑ Yi W, Clark PM, Mason DE, Keenan MC, Hill C, Goddard WA, Peters EC, Driggers EM, Hsieh-Wilson LC (Aug 2012). "Phosphofructokinase 1 glycosylation regulates cell growth and metabolism". Science. 337 (6097): 975–80. Bibcode:2012Sci...337..975Y. doi:10.1126/science.1222278. PMC   3534962 . PMID   22923583.
  20. ↑ Abrantes JL, Alves CM, Costa J, Almeida FC, Sola-Penna M, Fontes CF, Souza TM (Aug 2012). "Herpes simplex type 1 activates glycolysis through engagement of the enzyme 6-phosphofructo-1-kinase (PFK-1)". Biochim Biophys Acta. 1822 (8): 1198–206. doi: 10.1016/j.bbadis.2012.04.011 . PMID   22542512.
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