Lysosomal enzymes peptidase

This lysosomal enzyme [EC 3.4.22.1], also known as cathepsin Bl, is a member of the peptidase family Cl. The catalyzed reaction is the hydrolysis of peptide binds with a broad specificity. The enzyme prefers the ArgArg—Xaa bond in small peptide substrates (thus distinguishing this enzyme from cathepsin L). The enzyme also exhibits a peptidyl-dipeptidase activity, releasing C-terminal dipeptides from larger polypeptides. 

The lysosomal enzymes most relevant to our discussion are the peptidases and the nucleases. The peptidases, also referred to as the cathepsins, comprise at least eight exopeptidases and nine endopeptidases, which between them have a broad range of specificities that enable them to reduce any proteins or peptides to their constituent amino acids. 

Cat B is an abundant and ubiquitously expressed cysteine peptidase of the papain family and makes up a major fraction of lysosomal enzymes that is capable of degrading components of the extracellular matrix in various diseases [30-32]. Cat B is also a prognostic marker for several types of cancer [33], and increased expression and secretion of cat B has been shown to be involved in the migration and invasion of various tumours [34—36], The precise role of cat B in solid tumours is not fully understood, but it has been proposed to participate, along with other cysteine cathepsins, in metastasis, angiogenesis, and tumour progression [37], Indeed, cat B inhibitors reduce both tumour cell motility and invasiveness in vitro [38], Recently, metal complexes based on rhenium, gold and palladium were shown to be effective inhibitors of cat B [39-44],... 

Animal tissue is a soiuce of papain-related lysosomal cysteine peptidases that have been used in di- and tripeptide synthesis. Due to the insufficient homogenic preparations of cathepsin B, earlier reports of its synthetic activity have to be taken witii caution [16]. The availability of a recombinant production system for hiunan cathepsin B will allow experiments with pure enzyme. The endopeptidase cathepsin L from parasite Fasciola hepatica was expressed in yeast and used in the kinetically controlled synthesis of Cbz-Phe-Arg-Ser-NH starting from Cbz-Phe-Arg-OMe and H-Ser-NH in an aqueous medimn [31]. 

Careful examination of the yellowish sediment obtained after spinning down the crude mitochondrial fraction showed it was frequently overlaid with loosely packed, fluffy material —the fluffy layer. Experiments from de Duve s and, later, Novikoff s laboratories in the 1950s demonstrated that the lighter, lysosomal fraction was enriched in a number of hydrolases including acid phosphatase, aryl sulphatase, B glucuronidase, RNAase, and a peptidase, cathepsin. All the enzymes had optimal pHs in the acid range (pH 5-pH 6). Density... 

This enzyme [EC 3.4.16.5] (also known as serine-type carboxypeptidase I, cathepsin A, carboxypeptidase Y, and lysosomal protective protein) is a member of the peptidase family SIO and catalyzes the hydrolysis of the peptide bond, with broad specificity, located at the C-terminus of a polypeptide. The pH optimum ranges from 4.5 to 6.0. The enzyme is irreversibly inhibited by diisopropyl fluorophosphate and is sensitive to thiolblocking reagents. 

This lysosomal endopeptidase [EC 3.4.23.5] is similar to pepsin A, except that the specificity is narrower and will not hydrolyze the Gln" —His peptide bond in the B chain of insulin. The enzyme is a member of the peptidase family Al. 

This mammalian lysosomal endopeptidase [EC 3.4.22.16] is also known as aleurain, cathepsin B3, cathepsin BA, and benzoylarginineinaphthylamide hydrolase. A member of the peptidase family Cl, the enzyme also acts with an aminopeptidase activity, preferring Arg— Xaa peptide bonds. 

This peptidase family Cl enzyme [EC 3.4.22.15] is an lysosomal endopeptidase with specificity akin to papain. Cathepsin L displays a higher activity toward protein substrates than does cathepsin B. 

This enzyme [EC 3.4.14.1], also called cathepsin C and cathepsin J, catalyzes the hydrolysis of a peptide bond resulting in the release of an N-terminal dipeptide, XaaXbb-Xcc, except when Xaa is an arginyl or a lysyl residue, or Xbb or Xcc is a prolyl residue. This enzyme, a member of the peptidase family Cl, is a CF-dependent lysosomal cysteine-type peptidase. 

Proteolytic enzymes such as proteases and peptidases are ubiquitous throughout the body. Sites capable of extensive peptide and protein metabolism are not only limited to the liver, kidneys, and gastrointestinal tissue, but also include the blood and vascular endothelium as well as other organs and tissues. As proteases and peptidases are also located within cells, intracellular uptake is per se more an elimination rather than a distribution process [13]. While peptidases and proteases in the gastrointestinal tract and in lysosomes are relatively unspecific, soluble peptidases in the interstitial space and exopeptidases on the cell surface have a higher selectivity and determine the specific metabolism pattern of an organ. The proteolytic activity of subcutaneous tissue, for example, results in a partial loss of activity of SC compared to IV administered interferon-y. 

Chloride ions are known to be required for the activity of only a few enzymes — certain peptidases. These peptidases include angiotensin II (Bunning and Rior-dan, 1983,1987), an enzyme that participates in the regulation of salt metabolism, and the cathepstns. The cathepsins are located in lysosomes, organelles used for the hydrolysis of nutrients recently transported into the cell. 

Peptidases as integral components of cells have only been partly explored, e. g. lysosomal peptidases, granulocyte serine peptidases, membrane-bound peptidases, and enzymes of specialized tissues, such as the reproductive tract, skins, lens, muscle, pituitary, adrenals etc. Various ATP-dependent peptidases have been isolated. 

Quite recently, additional thiol proteinases have been found in lyso-somes. Cathepsin T, which catalyzed conversion of multiple forms of tyrosine aminotransferase, was demonstrated by Gk>hda and Pitot (20, 21). This enzyme does not cleave benzoylarginine-2-naphthylamide, a substrate for cathepsin B and cathepsin H. Melloni et al. (22, 23) reported the presence of a thiol peptidyl peptidase in a lysosomal membrane fraction of rabbit liver. In addition, cathepsin N with strong collagenolytic activity was found in bovine spleen and human placenta, although its lysosomal origin has not yet been demonstrated (24-26). 

Many authors have investigated the influence of ozone on pulmonary lysosomes and mitochondria. Lysosomes contain quite many enzymes, mainly hydrolases, such as protease, lipases, nucleases, phosphatases, phosphodiesterases, etc. Dillar et al. [273] have studied the changes in lysosome levels upon exposure of mice to ozone (0.7 ppm). The activity of pulmonary lysosomal cathepsin A, cathepsin D, acidic phosphatase, (3-N-acetylglucose aminidase, and benzyl arginine P-naphthylamide ami-dohydrolase was increased. This is due to inflammatory processes caused by ozone. The specific activity of protease and peptidase in the lung is enhanced when related to chronic obstructive genetic lack of a-1-antitrypsin factor. 

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