The proteolysis o protein degradation is a process by which the proteins of a cell can be completely degraded (down to their constituent amino acids) or partially (producing peptides). That is, it consists of the hydrolysis of one or more of the peptide bonds that hold their amino acids together..
This process can occur thanks to the participation of other proteins with enzymatic activity, in whose active sites the hydrolysis of the bonds occurs. It can also occur by non-enzymatic "methods", such as by the action of heat or substances with extreme pH (very acidic or very basic).
Protein degradation occurs in bacteria, animals and plants, but it is especially common in animals, especially at the level of the digestive system, since the digestion and intestinal absorption of the proteins ingested with the diet depends on it..
In addition, proteolysis is of utmost importance for the functional maintenance and regulation of multiple cellular processes and also has to do with the elimination of those proteins that present errors in translation, folding, packaging, importation, operation, etc..
It is important to note that it is an irreversible, highly effective process that also works in the “regulation of regulators”, since it not only eliminates those proteins that have “direct” biological activities, but also those that regulate other proteins or the expression of the corresponding genes.
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The internal proteins of a cell can be degraded randomly or selectively or, what is the same, in a controlled way or not. In turn, as previously commented, this process can occur by means of special enzymes or due to defined environmental conditions such as acidic and / or alkaline pH..
It is important to mention that any correctly translated, folded or packaged protein hides one or more degradation signal sequences that are "cryptic" and that can be exposed when the protein is structurally disturbed by temperature, pH, etc..
Ubiquitination (ubiquitin-proteasome system) is a system by which proteins can be selectively hydrolyzed after being specifically marked for degradation, a process that can occur both in the cytosol and in the cell nucleus.
This system has the ability to recognize and destroy labeled proteins in the nucleus and in the cytosol, as well as to degrade proteins that do not fold correctly during their translocation from the cytosol to the endoplasmic reticulum..
It works primarily by adding or conjugating the "target" proteins to a small protein or peptide of 76 amino acid residues, better known as ubiquitin. Those “marked” proteins by ubiquitination are degraded into small fragments by the 26S proteasome, a multi-subunit protease..
Autophagy is also considered by some authors as a form of proteolysis, with the distinction that it occurs within a closed membranous compartment that is directed towards the lysosomes (in animal cells), where the proteins contained within are degraded by lysosomal proteases.
The temperature, pH, and even the salt concentration of a medium can cause the hydrolysis of the peptide bonds that hold the amino acids of different types of proteins together, which occurs by destabilization and interruption of the bonds..
Proteolysis has many functions in living organisms. In particular, it has to do with protein turnover, whereby some specific protein molecules that were translated from one or more ribosomes are eventually degraded at different rates..
Proteins have a half-life that varies from a few seconds to a few months and the products of their degradation, whether regulated or not, mediated by enzymes or not, are generally reused for the synthesis of new proteins, which probably fulfill different functions..
This is what happens with proteins that are consumed with food, which are degraded in the gastrointestinal tract by proteases, including trypsin and pepsin; as well as with some cellular proteins when cells lack enough food to survive.
Intracellular proteolytic systems detect and eliminate "abnormal" proteins that are potentially toxic to cells, as they can interact with "physiologically inappropriate" ligands, in addition to producing aggregates that cause mechanical and physical impediments to normal cellular processes..
The accumulation of abnormal proteins inside the cell, either due to defects in the internal proteolytic system or for other reasons, is what many scientists consider to be one of the main causes of aging in multicellular living beings..
The partial proteolysis of many proteins from exogenous or foreign sources such as invading microorganisms, for example, is a fundamental process for the immune response system, since T lymphocytes recognize the short fragments, a product of proteolysis (peptides) that are presented to them in association with a set of surface proteins.
These peptides can come from the ubiquitination system, autophagic processes or uncontrolled proteolysis events..
Another function of limited or partial proteolysis is the modification of newly formed proteins, which functions as a "preparation" for their intra- or extracellular functions. This is true, for example, for certain hormones and for proteins involved in different metabolic processes..
Programmed cell death (apoptosis) also depends, to a large extent, on limited or partial “site-specific” proteolysis of intracellular proteins, which is mediated by a cascade of specific proteases called caspases..
Extracellular regulatory systems also depend on site-specific proteolysis, and the most prominent example is that of blood coagulation..
General or complete proteolysis also fulfills essential functions for the selective degradation of those proteins whose concentration must be carefully controlled depending on the physiological, metabolic or development of the cells..
Plants also use proteolytic processes to control many of their physiological and developmental aspects. It works, for example, in the maintenance of intracellular conditions and in the response mechanisms to stressful conditions such as drought, salinity, temperature, among others..
As in animals, proteolysis in plants collaborates in the activation and maturation of zymogens (inactive proteins), controls metabolism, homeostasis, programmed cell death processes, the development of tissues and organs, etc. In these organisms the pathway of proteolysis by ubiquitination is one of the most important.
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