Lysosomes digestive function

In addition to their plasma membrane eukaryotic cells also contain internal membranes that define a variety of organelles (fig. 17.2). Each of these organelles is specialized for particular functions The nucleus synthesizes nucleic acids, mitochondria oxidize carbohydrates and lipids and make ATP, chloroplasts carry out photosynthesis, the endoplasmic reticulum and the Golgi apparatus synthesize and secrete proteins, and lysosomes digest proteins. Additional membranes divide mitochondria and chloroplasts into even finer, more specialized subcompartments. Like the plasma membrane, organellar membranes act as barriers to the leakage of proteins, metabolites, and ions they contain transport systems for import and export of materials, and they are the sites of enzymatic activities as diverse as cholesterol biosynthesis and oxidative phosphorylation. 

Other lipoproteins and from cell membranes and converts it to cholesterol esters by the lecithin.-cholesterol acyltransferase (LCAT) reaction. Then HDL either directly transports cholesterol and cholesterol esters to the liver or transfers cholesterol esters to other lipoproteins via the cholesterol ester transfer protein (CETP) Ultimately, lipoprotein particles carry the cholesterol and cholesterol esters to the liver, where endocytosis and lysosomal digestion occur. Thus, reverse cholesterol transport (i.e., the return of cholesterol to the liver) is a major function of HDL. 

Most polymer-based carriers for the delivery of nucleic acid drugs must escape the endosomes before complete acidification, which activates lysosomal digestion. After the discovery of the powerful endosomal destabilization activity of PEI [66], many polymer-based carriers have mimicked the structure of PEI for endosomal escape. As explained in Sect. 3.2, the proton-sponge effect of xmprotonated tertiary amines and direct contact of protonated polyamines with the endosomal membrane are two possible mechanisms of endosomal disruption by PEI. Because pH-dependent protonation is critical in both mechanisms, polymers with a high density of protonable amines during the early endosomal acidification firom pH 7.4 to 5.5 are one of the main kinds of polymer-based carriers with an endosomal escape function. Like tertiary amines in PEI, protonable moieties with low p Ta values have been frequently introduced into the polymer-based carriers. An imidazole moiety with pA"a of around 6.0 was one such candidate. The introduction of polyhistidine with an imidazole moiety on a PLL backbone showed significant increase in endosomal escape efficiency [169]. 

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. 

The lysosomes are the cell s stomach, serving to break down various cell components. For this purpose, they contain some 40 different types of hydrolases, which are capable of breaking down every type of macromolecule. The marker enzyme of lysosomes is acid phosphatase. The pH optimum of lysosomal enzymes is adjusted to the acid pH value and is also in the range of pH 5. At neutral pH, as in the cytoplasm, lysosomal enzymes only have low levels of activity. This appears to be a mechanism for protecting the cells from digesting themselves in case lysosomal enzymes enter the cytoplasm at any time. In plants and fungi, the cell vacuoles (see p. 43) have the function of lysosomes. 

A primary function of the lysosome is to digest protein-containing particles derived from the extracellular space. One mechanism of delivery is the process of endocy-tosis. Endocytosis is the invagination of a group of occupied... 

The lysosomal enzymes The lysosomes are membrane vesicles ubiquitous to mammalian cells and contain a panoply of hydrolytic enzymes, estimated to be over 60 in number, that function to digest practically any biological macromolecule. They are important to the discussion of oral macromolecular drug delivery for two reasons. First, any macromolecules that escape digestion by the pancreatic and brush border enzymes are likely to be taken up into the epithelial cells by the process of endocytosis. In this process, the apical membrane invaginates and the target molecules enter endocytic vesicles that then fuse with the lysosomes and are subjected to intracellular hydrolysis by the lysosomal enzymes. Second, the sloughing-off of the epithelial cells means that the lysosomal enzymes will be released into the lumen of the intestine. They may be... 

A deficiency of lysosomal enzymes results in the inability to degrade the carbohydrate portions of proteoglycans or sphingolipids. Partially digested products accumulate in lysosomes. Tissues become engorged with these residual bodies, and their function is impaired. These diseases are often fatal. 

By contrast, in necrosis, severe physical, chemical, or bacterial damage causes a cell membrane to burst, releasing apoptotic mediators (Sect. 13.4.3) and proinflammatory cytokines into the stroma (Sect. 13.2.2). The cytosolic enzymes continue to make lactic acid in the absence of mitochondrial function, making the necrotic environment strongly acidic and activating lysosomal enzymes (Sect. 13.2.1) to digest the released cytosolic contents. Necrosis is discussed in relation to aggressive periodontitis (Chap. 14). 

The waste products are partially deposited on the Bruch s membrane (Young, 1987) in the form of drusen. The accumulation of lipofuscin in RPE cells appears detrimental to its function (Flood et al., 1984) and causes photoreceptor death (Dorey et ak, 1989). With age, the number of RPE cells decreases in the central retina, and they become pleomorphic (Dorey et ak, 1989). Other changes are also frequent. They include atrophy, depigmentation, hyperplasia, hypertrophy, and cell migration. The melanin concentration in the RPE cells decreases with age, especially in Caucasians, but also in blacks (Feeney-Burns et al., 1984). The melanin granules are slowly (over decades) digested by lysosomes (Bums and Feeney-Burns 1980). 

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. 

Lysosomes function in intracellular and extracellular digestion. They are capable of degrading most biomolecules. Lysosomes participate in the life of a cell in three fundamental ways (1) digestion of food molecules or other substances taken into the cell by endocytosis (a process illustrated in Figure 2.22), (2) digestion of worn out or unnecessary cell components, and (3) breakdown of extracellular material. 

The function of lysosomes is intracellular and extracellular digestion. These spherical, membranous organelles contain a group of enzymes called acid hydrolases, which degrade most biomolecules. 

Lysosomes are saclike organelles that function in intracellular and extracellular digestion. They contain digestive enzymes that can degrade most biomolecules. 

When a glycolipid cannot be degraded because of an enzymatic mutation, it accumulates in residual bodies (vacuoles that contain material that lysosomal enzymes cannot digest). Normal cells contain a small number of residual bodies, but in diseases of lysosomal enzymes, large numbers of residual bodies accumulate within the cell, eventually interfering with normal cell function. 

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