2.1. Pathways of proteins degradation

1. Degradation of tissue proteins. Principal causes of breakdown are: ageing of cells, external factors damage (toxicants, radiation), proteins denaturation, partial proteolysis of proteins during post-translational modification, digestion of digestive juices proteins, destruction of enzymes and hormones of protein nature when there is no need for them any longer.

Hydrolytic degradaration of proteins under the influence of proteolytic enzymes proceeds in any cell basically in lysosomes.

The time of protein half-life in a cell depends on the nature of its N-terminal amino acid. If it is easily attached to small protein ubiquitin in ATP-dependent reaction. Such ubiquity-binding protein is attacked by proteinases and degrades. Arg, lis, asp, asn attach to ubiquitine easily. Met, ser, ala, etc. are stabilizing hydrolytic degradation of proteins. Cytoplasmic proteins half-life time with N-terminal amino acid arg is 2 min, with met - 20 h.

2. Digestion of proteins.

Digestion of proteins begins in stomach and finishes in the upper small intestine. Proteolytic enzymes (proteinases) belong to hydrolases class. They are also named peptidases. Peptide bonds in protein molecule are broken down by hydrolysis reaction.

Conditions for digestion of proteins in stomach are active enzyme pepsin, hydrochloric acid.

Synthesis of hydrochloric acid is as follows: ions of chlorine from blood penetrate through the cell membrane and attach to hydrogen ions which are released with the dissociation of the carbonic acid formed in parietal cells. Then НС1 is excreted by parietal cells into stomach. Participation of АТP is supposed to take place.

Hydrochloric acid activates pepsin, creates optimal pH for its action; leads to proteins partial denaturation, it has bactericidal effect.

Gastric juice endopeptidases.

Pepsin is produced by the serous cells of the stomach in the inactive form (pepsinogen). It is converted into active pepsin under the influence of hydrochloric acid of gastric juice. The formed pepsin also activates pepsinogen. It is autocatalysis. The activation mechanism is partial proteolysis. The optimum рН of pepsin is near 2.

Rennin is present in babies' gastric juice. It converts casein to calcium paracaseinate which can be effectively digested by pepsin.

Secretion of hydrochloric acid and pepsinogen in the stomach is disturbed in many diseases of the gastrointestinal tract. More often the amount of hydrochloric acid is increased or decreased. High acidity occurs if there is stomach ulcer and a duodenum ulcer. Total absence of acid is observed in cases of atrophic gastritis; in these cases, as a rule, there is no pepsin either, i.e. there is no gastric juice formation (achylia).

Pancreatic juice endopeptidases.

Trypsin is synthesized in the form of trypsinogen. Trypsinogen activation occurs with the help of enteropeptidase, produced by the intestine cells. It eliminates N-terminal hexapeptide of trypsinogen. Thus, some trypsin is formed. The main part of trypsinogen is activated by autoactivation.

Proteinases are produced in an inactive form, since otherwise they would destroy the cell. The pancreas protects itself by another mechanism. It is the synthesis of proteins which are inhibitors of proteinases.

The other pancreatic pro-enzymes are activated by trypsin and also by partial proteolysis. As a result, endopeptidases (chymotrypsin and elastase) are formed, and exopeptidases (carboxypeptidases, aminopeptidases, and dipeptidases). Trypsin and chymotrypsin are the most active in slightly alkaline medium (pH 7,2-7,8). Dipeptidases hydrolyze peptide bonds in dipeptides formed at digestion.

The action of peptidases is relatively specific (Table 2). Sequential action of enzymes deprives proteins from species specificity and provides a full breakdown of proteins to amino acids.

Table 2