Phosphofructokinase (PFK) is a

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

enzyme that phosphorylates fructose 6-phosphate in

glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...

Function

The enzyme-catalysed transfer of a

phosphoryl group {{unreferenced, date=May 2015 A phosphoryl group is the chemical ion or radical: P+O32−, containing phosphorus and oxygen. (The correct chemical name for this −PO32− group is phosphonato, and phosphono for −PO3H2; as ''phosphoryl'' in ch ...

from Adenosine triphosphate, ATP is an important reaction in a wide variety of biological processes. Phosphofructokinase catalyses the phosphorylation of fructose-6-phosphate to fructose 1,6-bisphosphate, fructose-1,6-bisphosphate, a key regulatory step in the glycolytic pathway. It is Allosteric regulation, allosterically inhibited by ATP and allosterically activated by Adenosine monophosphate, AMP, thus indicating the cell's energetic needs when it undergoes the glycolytic pathway. PFK exists as a homotetramer in bacteria and Mammal, mammals (where each monomer possesses 2 similar Protein domain, domains) and as an octomer in yeast (where there are 4 alpha- (PFK1) and 4 beta-chains (PFK2), the latter, like the mammalian monomers, possessing 2 similar domains). This protein may use the morpheein model of allosteric regulation. PFK is about 300 Amino acid, amino acids in length, and structural studies of the Enzyme, bacterial enzyme have shown it comprises two similar (alpha/beta) lobes: one involved in ATP binding and the other housing both the substrate-binding site and the Allosteric regulation, allosteric site (a regulatory binding site distinct from the active site, but that affects enzyme activity). The identical tetramer subunits adopt 2 different conformations: in a 'closed' state, the bound Magnesium in biology, magnesium ion bridges the phosphoryl groups of the enzyme products (ADP and fructose-1,6-bisphosphate); and in an 'open' state, the magnesium ion binds only the Adenosine diphosphate, ADP, as the 2 products are now further apart. These Conformational change, conformations are thought to be successive stages of a Reaction mechanism, reaction pathway that requires subunit closure to bring the 2 molecules sufficiently close to react. The reverse reaction is Catalysis, catalyzed by the enzyme Fructose-1,6-bisphosphatase.

Phosphofructokinase family

PFK belongs to the phosphofructokinase B (PfkB) family of Kinase, sugar kinases. Other members of this family (also known as the Ribokinase family) include ribokinase (RK), adenosine kinase (AK), inosine kinase, and 1-phosphofructokinase. The members of the PfkB/RK family are identified by the presence of three conserved sequence Structural motif, motifs. The structures of several PfK family of proteins have been determined from a number of organisms and the Enzyme assay, enzymatic activity of this family of protein shows a dependence on the presence of pentavalent ions. PFK is found in isoform versions in skeletal muscle (PFKM), in the liver (PFKL), and from Platelet, platelets (PFKP), allowing for tissue-specific Gene expression, expression and function. It is still speculated that the isoforms may play a role in specific Glycolysis, glycolytic rates in the tissue-specific environments they are in. It has been found in humans that some human Immortalised cell line, tumor cell lines had increased glycolytic productivity and correlated with the increased amount of PFKL.

Clinical significance

Deficiency in PFK leads to glycogenosis type VII (Tarui's disease), an autosomal recessive disorder characterised by severe nausea, vomiting, muscle cramps and myoglobinuria in response to bursts of intense or vigorous exercise. Sufferers are usually able to lead a reasonably ordinary life by learning to adjust activity levels.

Regulation

There are two different phosphofructokinase enzymes in humans:

References

External links