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 In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...

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 ...

glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvic acid, pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The Thermodynamic free energy, free energy released in this process is used to form ...

Function

The enzyme-catalysed transfer of a

phosphoryl group A phosphoryl group is a trivalent group, consisting of a phosphorus atom (symbol P) and an oxygen atom (symbol O), where the three free valencies are on the phosphorus atom. While commonly depicted as possessing a double bond (P=O) the bonding i ...

from 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, known in older publications 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 glu ...

, a key regulatory step in the

glycolytic pathway Glycolysis is the metabolic pathway that converts glucose () into pyruvate and, in most organisms, occurs in the liquid part of cells (the cytosol). The free energy released in this process is used to form the high-energy molecules adenosine trip ...

. It is allosterically inhibited by ATP and allosterically activated by

AMP Amp or AMP may refer to: * Ampere, a unit of electric current, often shortened to amp * Amplifier, a device that increases the amplitude of a signal Arts and entertainment Music * After Midnight Project, Los Angeles alternative rock band * A ...

, 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 ...

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

and

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

s (where each

monomer A monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or two- or three-dimensional network in a process called polymerization. Classification Chemis ...

possesses 2 similar domains) and as an octomer in

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...

(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 di ...

model of

allosteric regulation In the fields of biochemistry and pharmacology an allosteric regulator (or allosteric modulator) is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the ...

. PFK is about 300

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s 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 the fields of biochemistry and pharmacology an allosteric regulator (or allosteric modulator) is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the p ...

(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 ...

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, 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 increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...

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 (Ado) leading to formation of Adenosine monophosphate ( AMP). In addition to its well-studied role in ...

(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. 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 muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

(PFKM), in the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

(PFKL), and from

platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...

s (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:

References

External links