Phosphofructokinase 1
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2008-04-10T23:05:18Z
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{{Protbox
|Name=Phosphofructokinase
|Photo=Phosphofructokinase 6PFK wpmp.png
|Caption=
|Gene_type=[[protein]] coding
|Molecular_weight= 82,000
|Structure=
|Type=Enzyme: [[Kinase]]
|Functions=converts [[fructose 6-phosphate]] + [[Adenosine triphosphate|ATP]] to [[fructose 1,6-bisphosphate]] + [[ADP]]
|Domains=
|Motifs=
|Alternative_products=
|Catalytic_activity=
|Cofactors=
|Enzyme_regulation=
|Diseases=
|Pharmaceuticals=
|Taxa=
|Cells= ubiquitous
|Location=
|Names=
|Pathways=[[Citric acid cycle]], [[Glycolysis]]
|Interactions=
|Pages=
|Review=
|ECnumber=2.7.1.11
|Names=6-Phosphofructokinase, 6-Phosphofructo-1-kinase, Fructose-6-P 1-Kinase, Fructose-6-phosphate 1-Phosphotransferase
}}
[[Image:Phosphofructokinase (active vs inactive form).png|thumb|Bacterial Phosphofructokinase: 3rd glycolysis enzyme (smaller than in Eukaryots). In yellow=sugars; in red=ATP-ADP; starred=regulatory sites (PDB code=4pfk)
([http://www.pdb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pdb50_4.html more details...])]]
'''Phosphofructokinase-1''' (PFK-1) is the most important regulatory [[enzyme]] ({{EC number|2.7.1.11}}) of [[glycolysis]]. It is an [[allosteric]] enzyme made of 4 subunits and controlled by several [[activator]]s and [[Enzyme inhibitor|inhibitor]]s. PFK-1 catalyzes one of the important "committed" steps of [[glycolysis]], the conversion of [[fructose 6-phosphate]] and [[Adenosine triphosphate|ATP]] to fructose 1,6-bisphosphate and [[Adenosine diphosphate|ADP]].
{{Enzymatic Reaction
|foward_enzyme=[[Phosphofructokinase-1]]
|reverse_enzyme=[[Fructose bisphosphatase]]
|substrate=α-<small>D</small>-[[fructose 6-phosphate]]
|product=α-<small>D</small>-[[fructose 1,6-bisphosphate]]
|reaction_direction_(foward/reversible/reverse)=reversible
|minor_foward_substrate(s)=[[adenosine triphosphate|ATP]]
|minor_foward_product(s)=[[ADP]]
|minor_reverse_substrate(s)=H<sub>2</sub>O
|minor_reverse_product(s)=P<sub>i</sub>
|substrate_image=beta-D-fructose-6-phosphate_wpmp.png
|product_image=beta-D-fructose-1,6-bisphosphate_wpmp.png
}}
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 [[monosaccharide]]s [[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.
== Regulation ==
PFK1 is [[allosterically]] inhibited by ATP and citrate (from the [[Citric_acid_cycle|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 (biochemistry)|substrate]] and an inhibitor.
PFK1 is [[allosterically]] activated by a high concentration of [[Adenosine monophosphate|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:
* {{Gene|PFKL}} - [[liver]]
* {{Gene|PFKM}} - [[muscle]]
* {{Gene|PFKP}} - [[platelet]]
==See also==
*[[PFK2]] (converts fructose 6-phosphate to fructose 2,6-bisphosphate through on site, or the opposite, on another site)
*[[PFP (enzyme)|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==
* {{MeshName|Phosphofructokinase-1}}
{{glycolysis}}
{{Kinases}}
{{Glycolysis enzymes}}
[[Category:EC 2.7.1]]
[[de:Phosphofructokinase]]
[[es:Fosfofructoquinasa-1]]
[[it:Fosfofruttochinasi]]
[[pt:Fosfofrutoquinase 1]]
[[zh:磷酸果糖激酶1]]