Phosphofructokinase 1

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Phosphofructokinase
Phosphofructokinase 6PFK wpmp.png
Other names: 6-Phosphofructokinase, 6-Phosphofructo-1-kinase, Fructose-6-P 1-Kinase, Fructose-6-phosphate 1-Phosphotransferase
Genetic data
Gene type: protein coding
Protein Structure/Function
Molecular Weight: 82,000 (Da)
Protein type: Enzyme: Kinase
Functions: converts fructose 6-phosphate + ATP to fructose 1,6-bisphosphate + ADP
Other
Cell types: ubiquitous
Pathway(s): Citric acid cycle, Glycolysis
Database Links
EC number: 2.7.1.11
File:Phosphofructokinase (active vs inactive form).png
Bacterial Phosphofructokinase: 3rd glycolysis enzyme (smaller than in Eukaryots). In yellow=sugars; in red=ATP-ADP; starred=regulatory sites (PDB code=4pfk) (more details...)

Phosphofructokinase-1 (PFK-1) is the most important regulatory enzyme (EC 2.7.1.11) of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by several activators and inhibitors. PFK-1 catalyzes one of the important "committed" steps of glycolysis, the conversion of fructose 6-phosphate and ATP to fructose 1,6-bisphosphate and ADP.

α-D-fructose 6-phosphate Phosphofructokinase-1 α-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.png
Pi H2O
 
  Fructose bisphosphatase

This step is subject to extensive regulation since it is not only irreversible, but also because the original substrate is forced to proceed down the glycolytic pathway after this step. This leads to a precise control of glucose and the other monosaccharides galactose and fructose going down the glycolysis pathway. Before this enzyme's reaction, glucose-6-phosphate can potentially travel down the pentose phosphate pathway, or be converted to glucose-1-phosphate and polymerized into the storage form Glycogen.

Contents

Regulation

PFK1 is allosterically inhibited by ATP and citrate (from the citric acid cycle) and its product. It is also inhibited by low pH to prevent the accumulation of hydrogen ions in muscle. The enzyme has two sites with different affinities for ATP which is both a substrate and an inhibitor.

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.

PFK is inhibited by glucagon through repression of synthesis.

The precise regulation of PFK 1 prevents glycolysis and gluconeogenesis from occurring simultaneously.

Genes

There are three phosphofructokinase genes in humans:

See also

  • PFK2 (converts fructose 6-phosphate to fructose 2,6-bisphosphate through on site, or the opposite, on another site)
  • PFP (reversibly interconverts fructose 6-phosphate and fructose 1,6-bisphosphate using inorganic pyrophosphate (rather than ATP)
  • fructose bisphosphatase (hydrolyses fructose 1,6-bisphosphate to fructose 6-phosphate)

External links

 v • d • e 
Glycolysis Metabolic Pathway
Glucose Hexokinase Glucose-6-phosphate Phosphoglucoisomerase Fructose 6-phosphate Phosphofructokinase Fructose 1,6-bisphosphate Fructose bisphosphate aldolase Dihydroxyacetone phosphate Glyceraldehyde 3-phosphate Triosephosphate isomerase Glyceraldehyde 3-phosphate Glyceraldehyde phosphate dehydrogenase
D-glucose wpmp.png ATP ADP Alpha-D-glucose-6-phosphate wpmp.png Beta-D-fructose-6-phosphate wpmp.png ATP ADP Beta-D-fructose-1,6-bisphosphate wpmp.png Glycerone-phosphate wpmp.png D-glyceraldehyde-3-phosphate wpmp.png D-glyceraldehyde-3-phosphate wpmp.png NAD+ + Pi NADH + H+
Biochem reaction arrow foward YYNN horiz med.png Biochem reaction arrow reversible NNNN horiz med.png Biochem reaction arrow foward YYNN horiz med.png Biochem reaction arrow reversible NNNN horiz med.png + Biochem reaction arrow reversible NNNN horiz med.png 2 Biochem reaction arrow reversible YYYY horiz med.png
NAD+ + Pi NADH + H+
1,3-Bisphosphoglycerate Phosphoglycerate kinase 3-Phosphoglycerate Phosphoglycerate mutase 2-Phosphoglycerate Enolase Phosphoenolpyruvate Pyruvate kinase Pyruvate Pyruvate dehydrogenase Acetyl-CoA
1,3-bisphospho-D-glycerate wpmp.png ADP ATP 3-phospho-D-glycerate wpmp.png 2-phospho-D-glycerate wpmp.png H2O Phosphoenolpyruvate wpmp.png ADP ATP Pyruvate wpmp.png CoA + NAD+ NADH + H+ + CO2 Acetyl co-A wpmp.png
2 Biochem reaction arrow reversible YYYY horiz med.png 2 Biochem reaction arrow reversible NNNN horiz med.png 2 Biochem reaction arrow reversible NYYN horiz med.png 2 Biochem reaction arrow foward YYNN horiz med.png 2 Biochem reaction arrow foward YYNN horiz med.png 2
ADP ATP H2O
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Phosphotransferases/kinases (EC 2.7)
2.7.1 - OH acceptorHexo- - Gluco- - Fructo- (Hepatic fructo-) - Galacto- - Phosphofructo- (1, 2) - Thymidine - NAD+ - Glycerol - Pantothenate - Mevalonate - Pyruvate - Deoxycytidine - PFP - Diacylglycerol - Bruton's tyrosine - Phosphoinositide 3 (Class I PI 3, Class II PI 3) - Sphingosine
2.7.2 - COOH acceptorPhosphoglycerate - Aspartate
2.7.3 - N acceptorCreatine
2.7.4 - PO4 acceptorPhosphomevalonate - Adenylate - Nucleoside-diphosphate
2.7.6 - P2O7Ribose-phosphate diphosphokinase - Thiamine pyrophosphokinase
2.7.7 - nucleotidyl-Integrase - PNPase - Polymerase - RNase PH - UDP-glucose pyrophosphorylase - Galactose-1-phosphate uridylyltransferase -Terminal deoxynucleotidyl transferase - RNA replicase - Reverse transcriptase (Telomerase) - Transposase
2.7.8 - other phos.N-acetylglucosamine-1-phosphate transferase
2.7.10-11 - proteinTyrosine - Serine/threonine-specific
v • d • e
Carbohydrate metabolism: glycolysis/gluconeogenesis enzymes
GlycolysisGlucokinase/Hexokinase/Glucose 6-phosphatase - Glucose isomerase - Phosphofructokinase 1/Fructose 1,6-bisphosphatase - Aldolase - Triosephosphate isomerase - Glyceraldehyde 3-phosphate dehydrogenase - Phosphoglycerate kinase - Phosphoglycerate mutase - Enolase - Pyruvate kinase
Gluconeogenesis onlyPyruvate carboxylase - Phosphoenolpyruvate carboxykinase - from lactate (Cori cycle): Lactate dehydrogenase - from alanine (Alanine cycle): Alanine transaminase
RegulatoryPhosphofructokinase 2/Fructose 2,6-bisphosphatase - Bisphosphoglycerate mutase
de:Phosphofructokinase

it:Fosfofruttochinasi

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