Proteinase activity

Proteinase-activated recqrtors (PARs) are a unique family of G-protein-coupled receptors (GPCRs) that are activated in response to serine proteinases. There are four PAR family members PAR-1 through to PAR-4. PAR-1 and PAR-3 respond to thrombin, PAR-2 responds to trypsin, whilst PAR-4 is sensitive to both thrombin- and trypsin-related proteinases. 

Proteinase-activated Receptors. Figure 1 Activation of proteinase-activated receptors (PARs) through proteolytic cleavage with serine proteinases (1) and independent of cleavage though PAR-specific activating peptides (2). 

Proteinase-activated Receptors. Table 1 Proteinase, peptide and non-peptide modulators of PAR activation... 

Hollenberg MD, Compton SJ (2002) International union of pharmacology. XXVII. Proteinase-activated receptors. Pharmacol Rev 54 203-217... 

MacFarlane SR, Seatter MJ, Kanke T et al (2001) Proteinase-activated receptors. Pharmacol Rev 53 245— 282... 

In some cases, receptor inactivation, e.g., of the V2 vasopressin receptor, is mediated by agonist-induced enzymatic cleavage of the GPCR. This nonendocytic proteolysis is promoted by a plasma membrane-associated metalloprotease. Proteinase-activated receptors (PARs) such as the thrombin receptor also follow a distinctly different pathway. PARs require the enzymatic cleavage of their N terminus, and the newly generated N terminus activates the receptor. Once... 

Trypsin is a major proteolytic digestive enzyme and the identified endogenous ligand for proteinase-activated receptor 2 (PAR 2). 

Moss ML, Jin SL, MiUa ME et al (1997) Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature 385 733-736 Nixon RA, Cataldo AM (2006) Lysosomal system pathways genes to neurodegeneration in Alzheimer s disease. J Alzheimers Dis 9 277-289 Noorbakhsh F, VergnoUe N, HoUenberg MD et al (2003) Proteinase-activated receptors in the nervous system. Nat Rev Neurosci 4 981-990... 

Proteinases and antiproteinases are part of the normal protective and repair mechanisms in the lungs. The imbalance of proteinase-antiproteinase activity in COPD is a result of either increased production or activity of destructive proteinases or inactivation or reduced production of protective antiproteinases. AAT (an antiproteinase) inhibits trypsin, elastase, and several other proteolytic enzymes. Deficiency of AAT results in unopposed proteinase activity, which promotes destruction of alveolar walls and lung parenchyma, leading to emphysema. 

Female NMRI mice were exposed to 100 ppm of hydrogen sulfide for 2 hours at 4-day intervals excitement was observed (Savolainen et al. 1980). Exposure also resulted in decreased cerebral ribonucleic acid (RNA), decreased orotic acid incorporation into the RNA fraction, and inhibition of cytochrome oxidase. An increase in the glial enzyme marker, 2, 3 -cyclic nucleotide-3 -phosphohydrolase, was seen. Neurochemical effects have been reported in other studies. Decreased leucine uptake and acid proteinase activity in the brain were observed in mice exposed to 100 ppm hydrogen sulfide for 2 hours (Elovaara et al. 1978). Inhibition of brain cytochrome oxidase and a decrease in orotic acid uptake were observed in mice exposed to 100 ppm hydrogen sulfide for up to 4 days (Savolainen et al. 1980). 

In an earlier report (J>), the decay of healthy yam tubers during storage was shown to be a result of catabolism of its proteins by an active a-glutamyl transpeptidase. There is also some alkaline proteolytic activity in the yam tuber (6), but little information is available on individual enzymes of the purine degradative pathway and on the properties of an alkaline proteinase that may function in yams during storage. This report describes the interrelation of five enzymes of ureide metabolism in fresh and stored yams, the release of ammonia in vitro by three of the enzymes that may provide an environment for alkaline proteinase activity in vivo, and the in vitro properties of an... 

Alkaline Proteinase Activity in Yams. The release of ammonia at several stages during ureide metabolism suggested a potential for alkaline conditions in yam tubers, rather than the usual neutral or acid conditions generally found in seeds and plants. 

Because yams are stored in open systems at ambient temperatures (usually warm), tuber tissue was examined for proteinase activity at 40°C. Some tubers had high apparent polyphenol oxidase activity upon peeling of the tubers (tissue turned deep purple at the peeled surface) so that PYP was added to extracts to combine with polyphenolic compounds and protect the proteinase from reacting with these compounds. Earlier studies had shown some inhibition of alkaline proteinase activity by ferric ion (24) so that EDTA was also added to the extracts to chelate any free iron. Two alkaline pH optima were found, at 9.0 and 10.5. The alkaline proteinases of white potatoes (Solanum tuberosum) have pH optima between 8.6 and 9 (25) and those of Carilla chocola tubers have pH optima between 8.0 and 9.5 (26,27T, suggesting that alkaline... 

Table 4. Substrate Specificity of Yam Tuber Alkaline Proteinase (Activity mg protein hydrolyzed)/10 mg enzyme/2hr).

Removal of the N- and C-terminal propeptides from fully folded procollagens occurs only after transport of procollagens across the Golgi stacks and results in collagen molecules that are then able to assemble into fibrils. C-proteinase activity is possessed by members of the tolloid family of zinc metalloproteinases,... 

Langsford et al. reported that Cellulomonas fimi culture supernatants contained cellulase and proteinase activities, for which there appeared to be a relationship. Glucose repressed the synthesis of both activities and cellulose induced both 60), Adding cellulose to Cellulomonas sp. (NRCC 2406) cultures stimulated growth and improved production of cellulases 61). Optimum conditions for growth and cellulase production were pH 6.5 and 30 C. The addition of glucose in the presence of cellulose inhibited growth. Several species of Cellulomonas have cellobiose phosphorylase. 

Normally, thrombin is present in the blood as an inactive proenzyme (see p. 270). Prothrombin is activated in two different ways, both of which represent cascades of enzymatic reactions in which inactive proenzymes (zymogens, symbol circle) are proteolytically converted into active proteinases (symbol sector of a circle). The proteinases activate the next proenzyme in turn, and so on. Several steps in the cascade require additional protein factors (factors 111, Va and Villa) as well as anionic phospholipids (PL see below) and Ca "" ions. Both pathways are activated by injuries to the vessel wall. 

Y. Kondoh, K. Shimizu, and K. Tanaka, Proteinase production and pathogenecity of Candida albicans II. Virulence for mice of C. albicans strains of different proteinase activity, Microbial. Immuno., 31, 1061, 1987. 

The gross proteolysis of casein is probably due solely to rennet and plasmin activity (O Keeffe et al. 1978). Bacterial proteases and peptides are responsible for subsequent breakdown of the large peptides produced by rennet and plasmin into successively smaller peptides and finally amino acids (O Keeffe et al. 1978). If the relative rate of proteinase activity by rennet, plasmin, and bacterial proteases exceeds that of the bacterial peptidase system, bitterness in the cheese could result. Bitter peptides can be produced from a,-,- or /3-casein by the action of rennet or the activity of bacterial proteinase on /3-casein (Visser et al. 1983). The proteolytic breakdown of /3-casein and the subsequent development of bitterness are strongly retarded by the presence of salt (Fox and Walley 1971 Stadhouders et al. 1983). The principal source of bitter peptides in Gouda cheese is 3-casein, and more particularly the C-terminal region, i.e., 3(193-209) and 3(193-207) (Visser et al. 1983). In model systems, bitter peptides are completely debittered by a peptidases system of S. cremoris (Visser et al. 1983). 

Proteases of L. bulgaricus and L. helveticus contribute to the ripening of Swiss cheese (Langsrud and Reinbold 1973). Strains of thermo-duric lactobacilli are generally more proteolytic than S. thermophilus (Dyachenko et al. 1970). The proteinase activity of L. bulgaricus is optimal at pH 5.2-5.8 and is associated with the cell envelope (Argyle et al. 1976). Some strains of L. brevis (Dacre 1953) andL. lactis (Bottazzi 1962) are also proteolytic. Surface-bound aminopeptidase from L. lactis, characterized by Eggiman and Bachman (1980), is activated by cobalt and zinc ions and has optimum activity at pH 6.2-7.2. A surface-bound proteinase and carboxypeptidase are also present in L. lactis. 

Brandsaeter, E. and Nelson, F. E. 1956A. Proteolysis by Lactobacillus casei. I. Proteinase activity. J. Bacteriol. 72, 68-72. 

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