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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
ATP ATP may refer to: Companies and organizations * Association of Tennis Professionals, men's professional tennis governing body * American Technical Publishers, employee-owned publishing company * ', a Danish pension * Armenia Tree Project, non ...
is an important reaction in a wide variety of biological processes. Phosphofructokinase catalyses the phosphorylation of
fructose-6-phosphate Fructose 6-phosphate (sometimes called the Neuberg ester) is a derivative of fructose, which has been phosphorylated at the 6-hydroxy group. It is one of several possible fructosephosphates. The β-D-form of this compound is very common in cells. ...
to
fructose-1,6-bisphosphate Fructose 1,6-bisphosphate, also known as Harden-Young ester, is fructose sugar phosphorylated on carbons 1 and 6 (i.e., is a fructosephosphate). The β-D-form of this compound is common in cells. Upon entering the cell, most glucose and fructos ...
, a key regulatory step in the glycolytic pathway. It is allosterically inhibited by ATP and allosterically activated by
AMP #REDIRECT Amp #REDIRECT Amp {{Redirect category shell, {{R from other capitalisation{{R from ambiguous page ...
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, thus indicating the cell's energetic needs when it undergoes the glycolytic pathway. PFK exists as a
homotetramer A tetrameric protein is a protein with a protein quaternary structure, quaternary structure of four subunits (tetrameric). Homotetramers have four identical Protein subunit, subunits (such as glutathione S-transferase), and heterotetramers are M ...
in
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
and mammals (where each
monomer In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification Mo ...
possesses 2 similar domains) and as an octomer in
yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...
(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 Morpheeins are proteins that can form two or more different homo-oligomers (morpheein forms), but must come apart and change shape to convert between forms. The alternate shape may reassemble to a different oligomer. The shape of the subunit ...
model of
allosteric regulation In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site. The site to which the effector binds is termed the ''allosteric site ...
. PFK is about 300
amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
in length, and structural studies of the 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 site (a regulatory binding site distinct from the active site, but that affects enzyme activity). The identical
tetramer A tetramer () (''tetra-'', "four" + '' -mer'', "parts") is an oligomer formed from four monomers or subunits. The associated property is called ''tetramery''. An example from inorganic chemistry is titanium methoxide with the empirical formula Ti ...
subunits adopt 2 different conformations: in a 'closed' state, the bound 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
ADP Adp or ADP may refer to: Aviation * Aéroports de Paris, airport authority for the Parisian region in France * Aeropuertos del Perú, airport operator for airports in northern Peru * SLAF Anuradhapura, an airport in Sri Lanka * Ampara Air ...
, as the 2 products are now further apart. These conformations are thought to be successive stages of a reaction pathway that requires subunit closure to bring the 2 molecules sufficiently close to react. The reverse reaction is
catalyzed Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
by the enzyme Fructose-1,6-bisphosphatase.


Phosphofructokinase family

PFK belongs to the phosphofructokinase B (PfkB) family of sugar kinases. Other members of this family (also known as the Ribokinase family) include
ribokinase In enzymology, a ribokinase () is an enzyme that catalyzes the chemical reaction :ATP + -ribose ⇌ ADP + -ribose 5-phosphate Thus, the two substrates of this enzyme are ATP and -ribose, whereas its two products are ADP and -ribose 5-phosph ...
(RK), adenosine kinase (AK),
inosine kinase In enzymology, an inosine kinase () is an enzyme that catalyzes the chemical reaction :ATP + inosine \rightleftharpoons ADP + IMP Thus, the two substrates of this enzyme are ATP and inosine, whereas its two products are ADP and IMP. Inosine k ...
, and
1-phosphofructokinase In enzymology, 1-phosphofructokinase () is an enzyme that catalyzes the chemical reaction :ATP + D-fructose 1-phosphate → ADP + D-fructose 1,6-bisphosphate Thus, the two substrates of this enzyme are ATP and D-fructose 1-phosphate, whereas ...
. The members of the PfkB/RK family are identified by the presence of three conserved sequence motifs. The structures of several PfK family of proteins have been determined from a number of organisms and the
enzymatic activity Enzyme assays are laboratory methods for measuring enzymatic activity. They are vital for the study of enzyme kinetics and enzyme inhibition. Enzyme units The quantity or concentration of an enzyme can be expressed in molar amounts, as with any ...
of this family of protein shows a dependence on the presence of pentavalent ions. PFK is found in isoform versions in
skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...
(PFKM), in the
liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
(PFKL), and from
platelets Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...
(PFKP), allowing for tissue-specific expression and function. It is still speculated that the isoforms may play a role in specific glycolytic rates in the tissue-specific environments they are in. It has been found in humans that some human 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:


See also

*
Phosphofructokinase deficiency Phosphofructokinase deficiency is a rare muscular metabolic disorder, with an autosomal recessive inheritance pattern. It may affect humans as well as other mammals (especially dogs). It was named after the Japanese physician Seiichiro Tarui (b. ...
( GSD type VII, Tarui's disease)


References


External links

* {{Portal bar, Biology, border=no EC 2.7.1 Moonlighting proteins Glycolysis enzymes