Phosphofructokinase (PFK) is a

kinase In biochemistry, a kinase () is an enzyme that catalysis, catalyzes the transfer of phosphate groups from High-energy phosphate, high-energy, phosphate-donating molecules to specific Substrate (biochemistry), substrates. This process is known as ...

enzyme that

phosphorylates In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, whi ...

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. ...

in glycolysis.

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 ...

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. ...

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 fructose ...

, a key regulatory step in the

glycolytic pathway 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) ...

. It is allosterically inhibited by ATP and allosterically activated by

AMP #REDIRECT Amp {{Redirect category shell, {{R from other capitalisation{{R from ambiguous page ...

, 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 quaternary structure of four subunits (tetrameric). Homotetramers have four identical subunits (such as glutathione S-transferase), and heterotetramers are complexes of different subunits. A tetramer ca ...

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 am ...

and

mammals Mammals () are a group of vertebrate animals constituting the class Mammalia (), characterized by the presence of mammary glands which in females produce milk for feeding (nursing) their young, a neocortex (a region of the brain), fu ...

(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 ...

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 consti ...

(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 sit ...

. PFK is about 300 amino acids 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 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 sit ...

(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 T ...

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 Reaction may refer to a process or to a response (disambiguation), response to an action, event, or exposure: Physics and chemistry *Chemical reaction *Nuclear reaction *Reaction (physics), as defined by Newton's third law *Chain reaction (disamb ...

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 recycl ...

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-phospha ...

(RK),

adenosine kinase Adenosine kinase (AdK; EC 2.7.1.20) is an enzyme that catalyzes the transfer of gamma-phosphate from Adenosine triphosphate (ATP) to adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse deri ...

(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 ...

, 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 m ...

(PFKM), in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

(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 i ...

(PFKP), allowing for tissue-specific

expression Expression may refer to: Linguistics * Expression (linguistics), a word, phrase, or sentence * Fixed expression, a form of words with a specific meaning * Idiom, a type of fixed expression * Metaphorical expression, a particular word, phrase, ...

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 A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

had increased glycolytic productivity and correlated with the increased amount of PFKL.

Clinical significance

Deficiency in PFK leads to

glycogenosis type VII 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. ...

(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