![Phosporylation of a serine residue, before and after shot](https://upload.wikimedia.org/wikipedia/commons/c/c5/Phosporylation_of_a_serine_residue%2C_before_and_after_shot.png)
In
chemistry, phosphorylation is the attachment of a
phosphate
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phosph ...
group to a molecule or an ion. This process and its inverse,
dephosphorylation
In biochemistry, dephosphorylation is the removal of a phosphate (PO43−) group from an organic compound by hydrolysis. It is a reversible post-translational modification. Dephosphorylation and its counterpart, phosphorylation, activate and de ...
, are common in
biology
Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...
and could be driven by natural selection.
[ ]
Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License. Protein phosphorylation often activates (or deactivates) many
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
s.
Glucose
Phosphorylation of
sugars is often the first stage in their
catabolism. Phosphorylation allows cells to accumulate sugars because the phosphate group prevents the molecules from diffusing back across their transporter. Phosphorylation of
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
is a key reaction in sugar metabolism. The chemical equation for the conversion of D-glucose to D-glucose-6-phosphate in the first step of
glycolysis is given by
:D-glucose + ATP → D-glucose-6-phosphate + ADP
:
ΔG° = −16.7 kJ/mol (° indicates measurement at standard condition)
Hepatic cells are freely permeable to glucose, and the initial rate of phosphorylation of glucose is the rate-limiting step in glucose metabolism by the liver (ATP-D-glucose 6-phosphotransferase) and non-specific hexokinase (ATP-D-hexose 6-phosphotransferase).
The role of glucose 6-phosphate in glycogen synthase: High blood glucose concentration causes an increase in intracellular levels of glucose 6 phosphate in liver, skeletal muscle and fat (adipose) tissue. (ATP-D-glucose 6-phosphotransferase) and non-specific hexokinase (ATP-D-hexose 6-phosphotransferase). In
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 ...
, synthesis of glycogen is directly correlated by blood glucose concentration and 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 ...
and
adipocytes, glucose has a minor effect on glycogen synthase. High blood glucose releases insulin, stimulating the trans location of specific glucose transporters to the cell membrane.
The liver's crucial role in controlling blood sugar concentrations by breaking down glucose into carbon dioxide and glycogen is characterized by the negative delta G value, which indicates that this is a point of regulation with. The hexokinase enzyme has a low Km, indicating a high affinity for glucose, so this initial phosphorylation can proceed even when glucose levels at nanoscopic scale within the blood.
The phosphorylation of glucose can be enhanced by the binding of Fructose-6-phosphate, and lessened by the binding fructose-1-phosphate. Fructose consumed in the diet is converted to F1P in the liver. This negates the action of F6P on glucokinase, which ultimately favors the forward reaction. The capacity of liver cells to phosphorylate fructose exceeds capacity to metabolize fructose-1-phosphate. Consuming excess fructose ultimately results in an imbalance in liver metabolism, which indirectly exhausts the liver cell's supply of ATP.
Allosteric activation by glucose 6 phosphate, which acts as an effector, stimulates glycogen synthase, and glucose 6 phosphate may inhibit the phosphorylation of glycogen synthase by cyclic AMP-stimulated protein kinase.
Phosphorylation of glucose is imperative in processes within the body. For example, phosphorylating glucose is necessary for insulin-dependent
mechanistic target of rapamycin
The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the ''MTOR'' gene. ...
pathway activity within the heart. This further suggests a link between intermediary metabolism and cardiac growth.
Glycolysis
Glycolysis is an essential process of glucose degrading into two molecules of
pyruvate, through various steps, with the help of different enzymes. It occurs in ten steps and proves that phosphorylation is a much required and necessary step to attain the end products. Phosphorylation initiates the reaction in
step 1 of the preparatory step (first half of glycolysis), and initiates step 6 of payoff phase (second phase of glycolysis).
Glucose, by nature, is a small molecule with the ability to diffuse in and out of the cell. By phosphorylating glucose (adding a phosphoryl group in order to create a negatively charged
phosphate group
In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthophosphoric acid .
The phosphate or orthophosphate ion is derived from phosph ...
), glucose is converted to glucose-6-phosphate and trapped within the cell as the cell membrane is negatively charged. This reaction occurs due to the enzyme hexokinase, an enzyme that helps phosphorylate many six-membered ring structures. Glucose-6-phosphate cannot travel through the cell membrane and is therefore coerced to stay inside the cell. Phosphorylation takes place in step 3, where fructose-6-phosphate is converted to fructose-1,6-bisphosphate. This reaction is catalyzed by phosphofructokinase.
While phosphorylation is performed by ATPs during preparatory steps, phosphorylation during payoff phase is maintained by inorganic phosphate. Each molecule of glyceraldehyde-3-phosphate is phosphorylated to form 1,3-bisphosphoglycerate. This reaction is catalyzed by GAPDH (glyceraldehyde-3-phosphate dehydrogenase). The cascade effect of phosphorylation eventually causes instability and allows enzymes to open the carbon bonds in glucose.
Phosphorylation functions as an extremely vital component of glycolysis, for it helps in transport, control and efficiency.
Protein phosphorylation
Protein phosphorylation is the most abundant
post-translational modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribos ...
in eukaryotes. Phosphorylation can occur on
serine,
threonine and
tyrosine
-Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the G ...
side chains (often called 'residues') through
phosphoester bond formation, on
histidine
Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the d ...
,
lysine and
arginine through
phosphoramidate bonds, and on
aspartic acid and
glutamic acid through mixed
anhydride linkages. Recent evidence confirms widespread histidine phosphorylation at both the 1 and 3 N-atoms of the imidazole ring.
Recent work demonstrates widespread human protein phosphorylation on multiple non-canonical amino acids, including motifs containing phosphorylated histidine, aspartate, glutamate, cysteine, arginine and lysine in HeLa cell extracts.
However, due to the chemical lability of these phosphorylated residues, and in marked contrast to Ser, Thr and Tyr phosphorylation, the analysis of phosphorylated histidine (and other non-canonical amino acids) using standard biochemical and mass spectrometric approaches is much more challenging
and special procedures and separation techniques are required for their preservation alongside classical Ser, Thr and Tyr phosphorylation.
The prominent role of protein phosphorylation in
biochemistry
Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...
is illustrated by the huge body of studies published on the subject (as of March 2015, the
MEDLINE
MEDLINE (Medical Literature Analysis and Retrieval System Online, or MEDLARS Online) is a bibliographic database of life sciences and biomedical information. It includes bibliographic information for articles from academic journals covering medic ...
database returns over 240,000 articles, mostly on ''protein'' phosphorylation).
ATP
ATP, the "high-energy" exchange medium in the cell, is synthesized in the
mitochondrion by addition of a third phosphate group to
ADP in a process referred to as
oxidative phosphorylation. ATP is also synthesized by
substrate-level phosphorylation during
glycolysis.
ATP is synthesized at the expense of solar energy by
photophosphorylation In the process of photosynthesis, the phosphorylation of ADP to form ATP using the energy of sunlight is called photophosphorylation. Cyclic photophosphorylation occurs in both aerobic and anaerobic conditions, driven by the main primary source of ...
in the
chloroplasts of plant cells.
Natural selection on phosphorylation
Whether natural selection has been involved in
Protein phosphorylation is less understood. A recent study has found that the interferon-regulatory factors family member 9 (IRF9) could be influenced by natural selection during Human species evolution.
This gene is one of the interferon-regulatory factors. The ancestral state (Ser129) in IRF9 is more frequently found in mammals, while the derived positively selected state (Val129) was fixed in human. This fixation should occur before the "out-of-Africa" event ~ 500,000 years ago. Thus the young amino acid (Val129) may serve as a dephosphorylation site of IRF9,
which may affect the immune response in human species.
See also
*
Moiety conservation
*
Phosida
*
Phosphoamino acid analysis
*
Phospho3D Phospho3D is a database of 3D structures of phosphorylation sites derived from Phospho.ELM.
See also
* Phospho.ELM
* Protein structure
Protein structure is the three-dimensional arrangement of atoms in an amino acid-chain molecule. Pr ...
*
Types of phosphorylation
References
External links
Functional analyses for site-specific phosphorylation of a target protein in cells (A Protocol)
{{Authority control
Cell biology
Cell signaling
Phosphorus
Post-translational modification