Phosphorylation is a fundamental process of biochemistry that occurs not only in the human organism but in all living organisms with a nucleus and bacteria. It is an indispensable component of intracellular signal transduction and an important way to control cell behavior. Mostly, components of proteins are phosphorylated, but other molecules such as sugars can also serve as substrates. At the chemical level of observation, phosphorylation of proteins results in a phosphoric acid ester bond.
What is phosphorylation?
Phosphorylation is a fundamental process of biochemistry that occurs in the human organism. Phosphorylation provides energy to the cell. The term phosphorylation refers to the transfer of phosphate groups to organic molecules – usually the amino acid residues that make up proteins. Phosphates have a tetrahedral structure consisting of a central atom of phosphorus and four surrounding covalently bonded oxygen atoms. Phosphate groups have a double negative charge. Their transfer to an organic molecule takes place through specific enzymes, so-called kinases. Consuming energy, these usually bind the phosphate residue to a hydroxy group of a protein, forming a phosphoric acid ester. However, this process is reversible, i.e. it can be reversed, again by certain enzymes. Such enzymes, which cleave off phosphate geuppen, are generally referred to as phosphatases. Both kinases and phosphatases each represent a distinct class of enzymes that can be further subdivided into subclasses according to various criteria, such as the nature of the substrate or the mechanism of activation.
Function and task
A crucial importance of phosphates, especially polyphosphates, in the organism is the provision of energy. The most prominent example is ATP (adenosine triphosphate), which is considered the main energy transmitter in the body. Therefore, energy storage in the human organism usually means the synthesis of ATP. To do this, a phosphate residue must be transferred to a molecule of ADP (adenosine diphosphate) so that its chain of phosphate groups linked by phosphoric anhydride bonds is extended. The resulting molecule is called ATP (adenosine triphosphate). The energy stored in this way is obtained from the renewed cleavage of the bond, leaving behind ADP. Cleavage of another phosphate is also possible, forming AMP (adenosine monophosphate). Each cleavage of a phosphate makes more than 30 kJ per mole available to the cell. Sugars are also phosphorylated during the course of human carbohydrate metabolism for energy reasons. Glycolysis is also referred to as a “collection phase” and a “gain phase” because energy in the form of phosphate groups must first be invested in the starting materials for the subsequent gain of ATP. In addition, glucose, for example, as glucose-6-phosphate, can no longer diffuse unhindered through the cell membrane and is thus fixed inside the cell, where it is needed for further important metabolic steps. In addition, phosphorylations and their reversal reactions, along with allosteric and competitive inhibition, represent the crucial mechanisms for regulating cell activity. In this process, proteins are mostly phosphorylated or dephosphorylated. The amino acids most commonly modified are serine, threonine, and tyrosine, which are present in proteins, with serine being involved in the overwhelming majority of phosphorylations. For proteins with enzyme activity, both processes can lead to activation or inactivation, depending on the structure of the molecule. Alternatively, (de)phosphorylation by transferring or withdrawing a double negative charge can also lead to a change in the conformation of the protein such that certain other molecules can bind to the affected protein domains or just not. An example of this mechanism is the class of G protein-coupled receptors. Both mechanisms play a prominent role in signal transduction within the cell and in the regulation of cellular metabolism. They can influence the behavior of a cell either directly via enzyme activity or indirectly, via altered transcription and translation of DNA.
Diseases and ailments
As universal and fundamental as the functions of phosphorylations are, the consequences when this reaction mechanism is impaired are manifold. A defect or inhibition of phosphorylation, usually triggered by a deficiency of protein kinases or their defectiveness, can lead to metabolic diseases, diseases of the nervous system and muscles, or individual organ damage, among others. First, nerve and muscle cells are often affected, which manifests itself in neurological symptoms and muscle weakness. On a small scale, some disorders of the kinases or phosphatases can be compensated for by the body, since in some cases several pathways are available for the transmission of a signal and thus the “defective site” in the signal chain can be bypassed. Then, for example, another protein replaces the defective one. Reduced enzyme efficiency, on the other hand, can be compensated for by simply producing more. Both internal and external toxins as well as genetic mutations are possible causes of a deficiency or malfunction of kinases and phosphatases. If such a mutation takes place in the DNA of the mitochondria, there are negative effects on oxidative phosphorylation and thus ATP synthesis, the main task of these cell organelles. One such mitochondrial disease is LHON (Leber’s hereditary optic neuropathy), in which there is rapid loss of vision, sometimes in combination with cardiac arrhythmias. This disease is inherited maternally, i.e., exclusively from the mother, since only her mitochondrial DNA is passed to the child, whereas the father’s is not.
