Phosphofructokinase

Phosphofructokinase is an important enzyme in the glycolytic pathway, which is a metabolic pathway that converts glucose into pyruvate. This enzyme catalyzes the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate, a key regulatory step in the glycolytic pathway.

Structure

Phosphofructokinase is a tetramer, composed of four subunits. Each subunit has a binding site for ATP, which is the substrate for the phosphorylation of fructose-6-phosphate. The enzyme also has allosteric sites for several other molecules, including AMP, ADP, and fructose-2,6-bisphosphate, which regulate the activity of the enzyme.

Function

The primary function of phosphofructokinase is to regulate the rate of glycolysis. By phosphorylating fructose-6-phosphate to fructose-1,6-bisphosphate, it commits the sugar to be further metabolized through the glycolytic pathway, rather than through other metabolic pathways such as the pentose phosphate pathway.

Regulation

Phosphofructokinase is regulated by several mechanisms. The enzyme is activated by AMP, ADP, and fructose-2,6-bisphosphate, which signal a high demand for ATP. Conversely, it is inhibited by ATP and citrate, which signal a low demand for ATP. This regulation ensures that glycolysis proceeds at a rate appropriate for the cell's energy needs.

Clinical significance

Mutations in the gene encoding phosphofructokinase can lead to Tarui disease, a type of glycogen storage disease. Symptoms of this disease include muscle weakness and exercise intolerance.

File:Phosphofructokinase 1 PDB 3pfk.png

3D structure of phosphofructokinase

See also

• Glycolysis
• Tarui disease
• Enzyme kinetics

References

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Glycolysis metabolic pathway

Glucose Hexokinase ATP ADP Glucose 6-phosphate Glucose-6-phosphate isomerase Fructose 6-phosphate Phosphofructokinase-1 ATP ADP Fructose 1,6-bisphosphate Fructose-bisphosphate aldolase Dihydroxyacetone phosphate + + Glyceraldehyde 3-phosphate Triosephosphate isomerase 2 × Glyceraldehyde 3-phosphate 2 ×  Glyceraldehyde-3-phosphate dehydrogenase NAD++ Pi NADH + H+ NAD++ Pi NADH + H+ 2 × 1,3-Bisphosphoglycerate 2 ×  Phosphoglycerate kinase ADP ATP ADP ATP 2 × 3-Phosphoglycerate 2 ×  Phosphoglycerate mutase 2 × 2-Phosphoglycerate 2 ×  Phosphopyruvate hydratase (enolase)   H2O   H2O 2 × Phosphoenolpyruvate 2 ×  Pyruvate kinase ADP ATP 2 × Pyruvate 2 ×

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