LYSOSOMES Lysosomes are a structurally heterogeneous group of organelles and vary dramatically in size and morphology. Lysosomes are spherical, membrane-bound organelles, 0.2-0.4 μm in diameter, that contain a variety of acid hydrolases. Of these, acid phosphatase is the most readily detected histochemically and is considered the “marker” enzyme for lysosomes. Lysosomes have two primary functions: Degradation of extracellular material ingested from the environment. Degradation of intracellular material no longer useful to the cell. However, leakage of hydrolytic enzymes can also result in undesirable destruction of cell components. This is called autolysis. Typical enzymes found within lysosomes are acid hydrolases that act in hydrolysis reactions, e.g. A. Proteases B. Nucleases C. Glycosidases D. Lipases, and others They are called acid hydrolases because they function at acid pH. With increased understanding of the function of the golgi apparatus, ER, pinosomes, phagosomes, and other membrane bound vesicles of the cell, we now realize that these organelles are all part of an intracellular system whose function is the packaging, processing (modification of molecules, digestion), and transport of materials either synthesized within the cell or taken into the cell by endocytosis. Types of Vesicles Found in Cellular Lysosomal Systems 1. Pinosomes - (50 - 250 nm) these are very small vesicles that form as invaginations of the cell membrane. The function of these invaginations is to endocytose small particulate and molecular matter from outside the cell. The invagination and its contents eventually pinch off from the cell membrane forming a cytoplasmic, membrane-bound vesicle known as a pinosome (or pinocytotic vesicle). These vesicles migrate through the cytoplasm. In some cases they fuse with each other, forming larger vesicles. In other cases, pinosomes will fuse with larger vesicles that are known as phagosomes or heterophagosomes emptying their contents into these larger vesicles. 2. Phagosomes - (0.5 - 5 um) these are larger vesicles than pinosomes. They are formed in one of two ways. In some cases phagosomes form from the fusion of a number of pinosomes. In other cases, these vesicles are the result of the cells phagocytic activity either via phagocytosis or as a result of autophagocytosis. 3. Small transport vesicles - membrane bound vesicles that transport materials synthesized by the rough ER to the golgi body. 4. Secretion vesicles - vesicles formed by the saccules of the golgi bodie‟s maturing face that contain materials that have been processed by in the Golgi body. 5. Lysosomes - are defined as membrane bound vesicles containing lytic enzymes that are utilized by the cell to break down (digest) materials within larger vesicles called phagosomes or autophagosomes. The enzymes within lysosomes are synthesized on the ribosomes of rough endoplasmic reticulum and packaged into their vesicular form by the Golgi body. Lysosomes are classified into three types: Primary lysosomes are those that are newly formed. Primary lysosomes, or protolysosomes, are newly produced organelles bounded by a single membrane and believed to be derived from the trans face of the Golgi apparatus. Although varying somewhat in size, primary lysosomes are typically about 100 nm in diameter. Primary lysosomes are virgin particles in that their digestive enzymes have not yet taken part in hydrolysis. Secondary lysosomes or heterolysosomes are those resulting from the fusion of a primary lysosome with a vesicle containing either extracellular or intracellular material. Two different kinds of secondary lysosomes can be identified: heterophagic vacuoles (also called heterolysosomes or phagolysosomes) and autophagic vacuoles (also called auto- lysosomes). Heterophagic vacuoles are formed by the fusion of primary lysosomes with cytoplasmic vacuoles containing extracellular substances brought into the cell by any of a variety of endocytic processes. Following fusion, the hydrolases of the primary lysosomes are released into the vacuole (variously called a phagosome or endosome). Autophagic vacuoles contain particles isolated from the cell‟s own cytoplasm, including mitochondria, microbodies, and smooth and rough fragments of the endoplasmic reticulum. Residual Bodies: Endocytosed substances and parts of autophagocytosed organelles that are not digested within the secondary lysosomes and transferred to the cytoplasm are retained (usually temporarily) within the vacuoles as residues. Lysosomes containing such residues are called residual bodies (sometimes also called telolysosomes or dense bodies). Residual bodies are large, irregular in shape, and are usually quite electron-dense. Residual bodies often fail to display the degree of hydrolytic activity associated with the primary and secondary lysosomes. Virtually all eucaryotic cells have lysosomal systems. Without them they could not exist. There would be no means to transport enzymes from one place to another in the cell and at the same time prevent those enzymes from catalysing cytoplasmic reactions. Secretion would be difficult and would be limited to diffusion, cellular rupture, or fragmentation (such as when megakaryocytes form platelets). An efficient system for recycling worn-out organelles would not exist. Intracellular digestion would be very difficult at best. Two cell types exhibit very active and well developed lysosomal systems. These are cells with secretory functions (neurons, acinar cells) and cells with digestive functions (macrophages, neutrophils). In secretory cells one would expect to find large numbers of secretory vesicles and autophagosomes in addition to the cellular organelles necessary for the synthesis of secretory product (rough ER, mitochondria) and the formation of the secretory vesicles (Golgi bodies). In digestive cells many pinosomes, phagosomes, primary and secondary (heterophagosomes, autophagosomes) lysosomes, and possibly residual bodies would be present, as well as Golgi bodies and rough ER. Functions of Lysosome 1. Lysosomes contain digestive enzymes which are used in digestion of reductant structure or damaged macromolecule from, within or outside the cell by autolysis. 2. Lysosome destroys foreign particles such as bacteria by phagocytosis. 3. It secretes the digestive enzymes. 4. Role in sperm penetration: During fertilization, the acrosome of sperm head discharges their lysosomal enzymes, which digest the limiting membrane of the ovum and help in the penetration of sperm into ovum. 5. Role in metamorphosis: during the process of metamorphosis of amphibians and tunicates, many embryonic tissues like gills, fins, tail etc. are digested by lysosomes and the products are utilized by other cells for their growth and differenciation. 6. Lysosomes play part in autophagy, autolysis, endocytosis and exocytosis. Autolysis is the self-digestion of a cell by releasing the contents of lysosome within the cell. For this reason, lysosomes sometimes called „suicide bags‟ or „self-breaking down‟. Autophagy is the process by which unwanted structures within the cell are engulfed and digested within lysosome. Endocytosis occurs by an infolding or extension of the cell surface membrane to form vesicles or vacuoles. It is of two types, these are: Phagocytosis – „cell eating‟. Material taken up is in solid form. Pinocytosis – „cell drinking‟. Material taken up is in liquid form. Exocytosis is the process in which waste materials may be removed from cells. It is the reverse of endocytosis. Lysosome formation The primary lysosomes are formed by budding from the trans face of the Golgi apparatus. The primary lysosomes are dispatched as either smooth or coated vesicles having a diameter of about 50-100 nm. After budding, the coat is lost. The acid hydrolases that are destined for lysosomes are synthesized by ribosomes of the rough ER in the vicinity of the Golgi bodies. Some of these hydrolases are discharged into the lumenal phase of the ER and others remain anchored in the ER membranes. Through either the dispatchment of tiny vesicles from the ER or via direct communication through cisternae, the hydrolases make their way to the cis face of the Golgi body. After purification and processing in successive Golgi cisternae, the hydrolases are released from the trans face of the Golgi apparatus in the form of primary lysosomes. Because of the intimate association between Golgi bodies, ER, and primary lysosomes, regions of cells containing these organelles are sometimes called “GERL” (i.e., “Golgi-Endoplasmic Reticulum-Lysosome”) complexes. THE "GERL" The acronym "GERL" stands for Golgi - Endoplasmic Reticulum - Lysosomal complex. These organelles form a system that when combined with the endocytotic and exocytotic pathways provide a means by which the cell can 1. process endocytosed and synthesized materials, 2. "Ingest" (endocytose via phagocytosis and pinocytosis) external substances and "Excrete" (exocytose) internal substances 3. Provide for the processing, recycling and removal of wastes from the cell Lysosomal storage diseases (LSDs) are a group of approximately 50 rare inherited metabolic disorders that result from defects in lysosomal function. Lysosomal storage disorders are caused by lysosomal dysfunction usually as a consequence of deficiency of a single enzyme required for the metabolism of lipids, glycoproteins or mucopolysaccharides. Gaucher disease: Most common of lysosomal storage diseases. Genetic disorder where there‟s accumulation of lipids in cells and organs results from a mutation in the gene that encodes a lysosomal enzyme required for the breakdown of glycolipids.
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