Peptidases are enzymes that can cleave peptide bonds of peptides and proteins catalytically by hydrolization, i.e., via the addition of an H2O molecule. Peptidases are active extracellularly and intracellularly. They are involved not only in the degradation of proteins and peptides for energy production and to obtain fragments for the construction of new proteins, but also in a variety of specialized functions such as activation of enzymatically acting proteins or neurotransmitters.
What is a peptidase?
The most important feature that distinguishes all peptidases is their ability to dissolve peptide bonds between two amino acids via hydrolization. This involves the attachment of an H2O molecule and is virtually equivalent to the reverse of the peptidation process. Proteins and peptides are composed of a stringing together of amino acids via peptide bonds. The only difference between peptides and proteins is that proteins consist of chains of more than about 100 amino acids, while peptides have shorter chains of at least two to about a maximum of 100 amino acids. The large number of peptidases specialized for specific targets and catalytic processes poses challenges for a generally applicable classification. Basically, a distinction can be made between exopeptidases and endopeptidases. Exopeptidases attack peptide chains either from the N-terminal end (aminopeptidases) or from the C-terminal end (carboxypeptidases) and are specialized to cleave off one amino group each or whole peptide fragments with two, three or more amino acids. Endopeptidases are specialized to attack specific sites of the proteins. This often involves the process of activating an enzyme, comparable to the removal of a locking lever. Peptidases can be classified according to the international EC nomenclature.
Function, action, and tasks
Peptidases perform several different basic functions. The most prominent function and task, in the catabolic branch of metabolism, is the fragmentation of proteins in the diet for absorption through the intestinal mucosa. However, the function of protein fragmentation is also required within the body for the breakdown of endogenous proteins for the purpose of energy production or for the generation of protein fragments for the anabolic part of metabolism to build new proteins. Another function and task is to activate certain proteins after synthesis by splitting off a certain amino acid the protein. So-called signal peptidases detach signal peptides from proteins. This ensures that intracellularly produced proteins are transported to their intended site of action. An important task for peptidases is their involvement in the synthesis of antigens. To perform this function, peptidases join together to form a peptidase complex, the proteasome. Intracellular peptidases are found in almost all cell compartments and cell organelles, where they are responsible for maintaining protein balance, among other functions. Peptidases also perform important functions within the coagulation process and are thus partly responsible for the rapid closure of a wound without the formation of blood clots, which can be carried along with the blood flow and lead to infarcts.
Formation, occurrence, properties, and optimal values
Peptidases occur in almost all tissues as extracellular peptidases and in virtually all cells as intracellular peptides, each with different roles but similar functions and actions. Extracellular peptidases are secreted by exocrine glands such as the salivary glands in the mouth, the gastric mucosa and especially by the pancreas. The process of protein breakdown already begins in the mouth and continues in the stomach. The final breakdown of proteins into defined fragments that can be taken up and absorbed by endothelial cells of the intestinal mucosa occurs mainly in the duodenum, the first segment of the small intestine after the stomach. In the small intestine, precursors of digestive enzymes called zymogens are activated by peptidases into the bioactive form by cleavage of certain amino acids. The indication of reference values or optimal concentrations of peptidases can only ever refer to a specific peptidase and, at best, allows conclusions to be drawn about the presence of certain problems only by comparison with some other laboratory parameters and subsequent differential diagnosis.For example, an elevated leucine amino peptidase (LAP) level does not yet indicate the presence of cholestasis, a congestion of digestive enzymes. LAP levels range from 16-32 units per liter in women and 11-35 units per liter in men. If the values are highly elevated, they should be clarified with the concentrations of certain liver enzymes in the blood such as alkaline phosphatase, gamma-GTP, and some other values.
Diseases and disorders
Enzymes overall represent the largest group of substances within proteins. Within enzymes, peptidases and lipases occupy an important place as digestive enzymes. The large number of peptidases – more than 250 different peptidases are known – means that metabolic disorders can also occur that are acquired, i.e., caused by an unbalanced diet, by disease, or by toxins. On the other hand, it can be assumed that the complex interplay of enzyme metabolism can also be influenced and impaired by gene mutations. The symptoms and risks resulting from metabolic disorders can range from mild to severe. Only recently have the links between non-specific symptoms and specific disorders in the metabolism of peptidases and other enzymes been explored. Decreased peptidase activity in the intestine leads to increased uptake of longer-chain peptides, which are formed as fragments from proteins, into the blood and to increased excretion via the kidneys, so that the facts can be established relatively easily by urinalysis. Interestingly, decreased peptidase activity has been associated with diseases such as ADD, ADHD, schizophrenia, autism, and depression.
