Lysosomal proteins

Q Rough endoplasmic reticulum (ER) functions in the synthesis, processing, and sorting of secreted proteins, lysosomal proteins, and certain membrane. 

The trans Golgi network (TGN) is a major branch point In the secretory pathway where soluble secreted proteins, lysosomal proteins, and In some cells membrane proteins destined for the basolateral or apical plasma membrane are segregated Into different transport vesicles. 

One limitation of enzyme replacement therapy is the targeting of enzyme proteins to appropriate sites of substrate accumulation. Administration of a cholesterol esterase conjugated to albumin results in the degradation of pathologic cholesterol ester accumulations within the lysosomes of fibroblasts from a patient with cholesterol ester storage disease (246). 

Mammals, fungi, and higher plants produce a family of proteolytic enzymes known as aspartic proteases. These enzymes are active at acidic (or sometimes neutral) pH, and each possesses two aspartic acid residues at the active site. Aspartic proteases carry out a variety of functions (Table 16.3), including digestion pepsin and ehymosin), lysosomal protein degradation eathepsin D and E), and regulation of blood pressure renin is an aspartic protease involved in the production of an otensin, a hormone that stimulates smooth muscle contraction and reduces excretion of salts and fluid). The aspartic proteases display a variety of substrate specificities, but normally they are most active in the cleavage of peptide bonds between two hydrophobic amino acid residues. The preferred substrates of pepsin, for example, contain aromatic residues on both sides of the peptide bond to be cleaved. 

Cathepsin D Spleen, liver, and many other animal tissues Lysosomal digestion of proteins... 

A problem with employment of ASON in a larger clinical setting is their poor uptake and inappropriate intracellular compartmentalization, e.g., sequestration in endosomal or lysosomal complexes. In addition, there is a need for a very careful selection of the ASON-mRNA pair sequences that would most efficiently hybridize. To date, several computer programs are used to predict the secondary and tertiary structures of the target mRNA and, in turn, which of the mRNA sequences are most accessible to the ASON. However, even with this sophisticated techniques, the choice of base-pairing partners still usually includes a component of empiricism. Despite these principal limitations, it has become clear that ASON can penetrate into cells and mediate their specific inhibitory effect of the protein synthesis in various circumstances. 

Cathepsins are intracellular proteinases that reside within lysosomes or specific intracellular granules. Cathepsins are used to degrade proteins or pqffides that are internalised from the extracellular space. Some cathepsins such as cathepsin-G or cathepsin-K may be released from the cell to degrade specific extracellular matrix proteins. All cathepsins except cathepsin-G (serine) and cathepsin-D (aspartyl) are cysteine proteinases. 

COPD is a chronic inflammatory disease that results from prolonged and repeated inhalation of particles and gases, chronic (or latent) infection or an interaction of these factors. In many cases, the inflammation persists even when the exposure (in most cases smoking) is stopped. Prominent among the infiltrating leukocytes are neutrophils, CD8+ lymphocytes (Co-receptor for the T-cell receptor. CD8+ is specific for the class IMHC protein. It is expressed on the surface of cytotoxic T-cells and natural killer cells.) and CD68+ monocytic cells (A lysosomal antigen. All cells that rich in... 

Mucolipin, also known as mucolipin 1 or mucolipidin (encoded by the MCOLN1 gene), is a TRP channel-related membrane protein, most probably residing in intracellular membranes. Is defective in mucolipidosis type IV disease, a developmental neurodegenerative disorder characterized by lysosomal storage disorder and abnormal endocytosis of lipids. The fimction of mucolipin is unknown. 

Disorders caused by mislocalization of lysosomal proteins (e.g., mutations in the N-acetylglucosamine 1-phosphotransferase leading to inclusion cell disease). 

Transport of proteins and lipids occurs between the organelles of the secretory pathway, i.e. endoplasmic reticulum (ER), Golgi, endosomes, lysosomes and the plasma membrane. 

In eukaryotes, anabolic and catabolic pathways that interconvert common products may take place in specific subcellular compartments. For example, many of the enzymes that degrade proteins and polysaccharides reside inside organelles called lysosomes. Similarly, fatty acid biosynthesis occurs in the cytosol, whereas fatty... 

LDL (apo B-lOO, E) receptors occur on the cell surface in pits that are coated on the cytosolic side of the cell membrane with a protein called clathrin. The glycoprotein receptor spans the membrane, the B-lOO binding region being at the exposed amino terminal end. After binding, LDL is taken up intact by endocytosis. The apoprotein and cholesteryl ester are then hydrolyzed in the lysosomes, and cholesterol is translocated into the cell. The receptors are recycled to the cell surface. This influx of cholesterol inhibits in a coordinated manner HMG-CoA synthase, HMG-CoA reductase, and, therefore, cholesterol synthesis stimulates ACAT activ-... 

Proteins are degraded by both ATP-dependent and ATP-independent pathways. Ubiquitin targets many intracellular proteins for degradation. Liver cell surface receptors bind and internalize circulating asialoglycoproteins destined for lysosomal degradation. 

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