Lysosomal enzymes protease

Cathepsin K (Cat K) is a member of the CA1 family of lysosomal cysteine proteases. This family is comprised of 11 human members (cathepsins B, C, F, H, K, L, O, S, V, W, Z) which share a common papain-like structural fold and a conserved active site Cys-Asn-His triad of residues [1-3]. These enzymes are synthesized as pre-pro-enzymes and are converted from the catalytically inactive zymogen into the active form in acidic lysosomal environment. In some cases, cathepsins are also secreted in the active form from cells. The sequence identity of... 

C5a is inactivated by the myeloperoxidase-H202 system, which oxidises a methionine residue (Met 70) on the molecule group A streptococcal endo-proteinases also abolish chemotactic activity of C5a and related compounds. Neutrophil lysosomal enzymes (e.g. elastase and cathepsin G) also destroy C5a chemotactic activity, but as these proteases are inhibited by the serum antiproteinases, a -antiproteinase and a2-macroglobulin, the physiological role of neutrophilic proteases in the inactivation of C5a is questionable. Two chemotactic factor inactivators have been found in human serum an a-globulin that specifically and irreversibly inactivates C5-derived chemotactic factors, and a / -globulin that inactivates bacterial chemotactic factors. These activities are heat labile (destroyed by treatment at 56 °C for 30 min) and are distinct from those attributable to anaphylatoxin inactivator. An apparently specific inhibitor of C5-derived chemotactic activity has also been described in human synovial fluid and peritoneal fluid. This factor (molecular mass of 40 kDa) is heat stable and acts directly on C5a. 

Previous studies have shown that muscle lysosomal hydrolases are released early in the postmortem period due to a decrease in intracellular ATP concentrations. The decreased intracellular ATP level causes the rupture of the lysosomal membrane (14), releasing hydrolytic enzymes (proteases, lipases, and glycosidases) that further potentiate the weakening of membrane integrity and cellular function. Furthermore, as the acidosis increases (due to the anaerobic conditions associated with cellular death) the intramuscular pH to levels reach that which are optimal for the activity of several lysosomal thiol proteinases. 

Many biological cells contain degradative enzymes (proteases) that catalyze the hydrolysis of peptide linkages. In the intact cell, functional proteins are protected from these destructive enzymes because the enzymes are stored in cell organelles (lysosomes, etc.) and released only when needed. The proteases are freed upon cell disruption and immediately begin to catalyze the degradation of protein material. This detrimental action can be slowed by the addition of specific protease inhibitors such as phenylmethyl-sulfonyl fluoride or certain bioactive peptides. These inhibitors are to be used with extreme caution because they are potentially toxic. 

In contrast to parasitic helminths, very few proteases of the snail hosts have been characterized at the functional and molecular levels (Sajid and McKerrow, 2002). Proteolytic enzymes have been implicated in playing a role in parasite destruction or survival in the snail host. Elevation of lysosomal enzyme activity in... 

How ever, it is important to acknowledge that apoptosis is not the only means for neurons to die. Death of adult neurons in response to pathological challenges also occurs by necrosis, the unregulated cell death mechanism. Necrosis is mediated by increase in intracellular calcium that catalyses activation of Ca + -dependent cystine proteases like, cathepsins and calpains, w hich primarily compromise lysosomal integrity. Subsequently, these cystine proteases in the company of released lysosomal enzymes dismantle structural netw ork of neuron. Additionally, the intracellular pH also plays a major role in necrosis (Syntichaki and Tavemarakis, 2003). 

The cytoplasmic droplet in bull and ram serum is spherical with a diameter of approximately 3 /x. When viewed by phase contrast microscopy, it has a dark granulated region electron microscopy reveals that this region consists of vesicles and membranous or tubular structures. The concentration of acid phosphatase in droplets is 4.3 /xg nitrophenol liberated per hour per 10 particles, much higher than the activity, 0.2 /xg nitrophenol liberated per hour per 10 spermatozoa. Ribonuclease, acid protease, y3-glueuronidase showed similar ratios. Dott and Dingle (D14) submitted additional information which indicated that in the bull and, to a lesser extent in the ram, the lysosomal enzymes cease to be associated with the spermatozoon during its maturation. 

Another important RPE function that might be altered by senescence, or by other stresses, is lysosomal enzyme actixfity. RPE cells digest the continuously growing outer segments (Sharma and Ehinger, 2003). A decrease in lysosomal enzyme activity has been reported to accompany the aging process. Impairment of RPE lysosomal enzymatic activity could play an important role in the development of AMD (Berson, 1973 Yamada et al. 1990 Boulton et al., 1994). Cathepsin D (CatD) is an aspartic protease lysosomal enzyme involved in opsin proteolysis. CatD is present in various retinal cell types, especially the RPE cells (Yamada et al., 1990). Its impairment could play a role in AMD. 

Lysosomal system - The primary lysosomes, budded from the Golgi complex, are bags of degradative enzymes. Over 50 different hydrolytic enzymes are contained in lysosomes, including proteases, nucleases, lipases, and carbohydrate-cleaving enzymes. 

The endoglycosidase has a molecular weight of around 80,000 (6, 7). Other lysosomal enzymes are the exoglycosi-dases, the proteases, collagenase, nuclease, sulfatases, and phosphatases. The release of hyaiuronidase from the cancer cell is usually accompanied by a release of increased amounts of other lysosomal enzymes, as has been demonstrated for a wide variety of experimental and human tumors (93, 110, 120, 172, 190, 282, 292, 316). 

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