Role of proteolytic enzymes in biological regulation (a review).

Abstract

Many enzymes, hormones, and other physiologically active proteins are synthesized as inactive precursors (zymogens) that are subsequently converted to the active form by the selective enzymatic cleavage (limited proteolysis) of peptide bonds. The ultimate agency of activating enzymatic function is limited proteolysis, either in a single activation step or in a consecutive series (cascade). The specificity of each activation reaction is determined by the complementarity of the zymogen substrate and the active site of the attacking protease. The sequence of consecutive activation reactions is regulated by the specificity of each enzyme, whereas the degree of amplification of the initial stimulus is determined by the efficiency of each activating step.Zymogen activation produces a prompt and irreversible response to a physiological stimulus, and is capable of initiating new physiological functions. Typical examples are the processes of blood coagulation, fibrinolysis, complement activation, hormone production, metamorphosis, rtilization, supramolecular assembly, and digestion. The zymogens of the pancreatic serine proteases, in particular, have served as models for detailed studies of the nature of the molecular changes that are involved in the dramatic increase in enzymatic activity that ensues upon limited proteolysis of the zymogen. In recent years, it has become evident that many proteins are synthesized as inactive precursors or zymogens and that these are subsequently converted to physiologically active forms by the selective enzymatic cleavage of peptide bonds. This process is known as zymogen activation, a term which initially was applied to the activation of precursors of proteolytic enzymes such as trypsinogen, chymotrypsinogen, or procarboxypeptidase (1). It is now apparent that the same type of reaction is involved in a great variety of biological processes, such as blood coagulation, fibrinolysis, complement reaction, hormone production, development, differentiation, and supramolecular assembly, all of which involve zymogen activation in one or more steps (2-9). In the present article, we shall attempt to show that activation by limited proteolysis is indeed an important control element which can initiate new physiological functions or regulate preexistent ones.Virtually all zymogen activation reactions require the en- The position of zymogen activation in the overall scheme of physiological control processes is diagrammatically shown in Fig.

Removal of the adhesive gum layer surrounding naturally fertilised ballan wrasse (Labrus bergylta) eggs

“…In this study, it was observed that the enzyme treatment liberated the eggs by actually breaking down and removing the outer gum layer surrounding the eggs suggesting that higher hatch rates may arise from treated eggs that have less of a barrier surrounding the chorion to break through. The breakdown of the adhesive gum layer was an expected result because the general chemical function of proteolytic enzymes is to digest or breakdown the long chain molecules into amino acids (Neurath & Walsh, 1976). However, the mechanism by which the gum layer removal occurred was both interesting and unexpected; as enzyme exposure progressed, the gum layer started to swell and become less structured and instead of breaking down or dissolving into pieces the gum layer swelled until it was completely bloated, then came off as a single casing, leaving a clean non-adhesive egg.…”

Serine carboxypeptidases. A review

“…Several zymogens, e.g. chymotrypsinogen, have been shown to be activated by a proteolytic cleavage of internal peptide bonds located between two disulfide bridges, such that the active species comprises two peptide chains linked by disulfide bridges (145) and this could similarly account for the existence of two peptide chains in the serine carboxypeptidases from plants. The existence of only a single peptide chain in the active enzymes from fungi suggests that potential zymogens of these enzymes might be activated by cleavage of an internal peptide bond located on the N-terminal side of the disulfide bridges.…”

Identification of inhibitors using a cell-based assay for monitoring Golgi-resident protease activity

“…Proteolytic processing is modulated both temporally and positionally and contributes to protein activation and sub-cellular localization [6]. Proteases involved in maturation of secretory proteins typically reside in the Trans-Golgi Network (TGN) where they proteolytically process newly formed proteins from the endoplasmic reticulum before packaging into secretory vesicles.…”