Selasa, 21 Juni 2011

Lysosomes

Lysosomes are sites of intracellular digestion and turnover of cellular components. Lysosomes (Gr. lysis, solution, + soma, body) are membrane-limited vesicles that contain a large variety of hydrolytic enzymes (more than 40) whose main function is intracytoplasmic digestion (Figures 2–24, 2–25, and 2–26). Lysosomes are particularly abundant in cells exhibiting phagocytic activity (eg, macrophages, neutrophilic leukocytes). Although the nature and activity of lysosomal enzymes vary depending on the cell type, the most common enzymes are acid phosphatase, ribonuclease, deoxyribonuclease, proteases, sulfatases, lipases, and beta-glucuronidase. As can be seen from this list, lysosomal enzymes are capable of breaking down most biological macromolecules. Lysosomal enzymes have optimal activity at an acidic pH.

Figure 2-24
Photomicrograph of a kidney tubule whose lumen appears in the center as a long slit. The numerous dark-stained cytoplasmic granules are lysosomes (L), organelles abundant in these kidney cells. The cell nuclei (N), some showing a nucleolus, are also seen in the photograph as dark-stained corpuscles. Toluidine blue stain. High magnification.

Figure 2-25
Electron micrograph of a macrophage. Note the abundant cytoplasmic extensions (arrows). In the center is a centriole (C) surrounded by Golgi cisternae (G). Secondary lysosomes (L) are abundant. x15,000.

Figure 2-26
Electron micrograph showing four dark secondary lysosomes surrounded by numerous mitochondria.

Lysosomes, which are usually spherical, range in diameter from 0.05 to 0.5 micrometer and present a uniformly granular, electron-dense appearance in electron micrographs. In a few cells, such as macrophages and neutrophilic leukocytes, primary lysosomes are larger, up to 0.5 micrometer in diameter, and thus are just visible with the light microscope.

The enveloping membrane separates the lytic enzymes from the cytoplasm, preventing the lysosomal enzymes from attacking and digesting cytoplasmic components. The fact that the lysosomal enzymes are practically inactive at the pH of the cytosol (~7.2) is an additional protection of the cell against leakage of lysosomal enzymes.

Lysosomal enzymes are synthesized and segregated in the RER and subsequently transferred to the Golgi complex, where the enzymes are modified and packaged as lysosomes. These enzymes have oligosaccharides attached to them with one or more of the mannose residues phosphorylated at the 6´ position by a phosphotransferase. There are receptors for mannose 6-phosphate-containing proteins in the RER and Golgi complex that allow these proteins to be diverted from the main secretory pathway and segregated in lysosomes.

Lysosomes that have not entered into a digestive event are identified as primary lysosomes.

Lysosomes can digest material taken into the cell from its environment. The material is taken into a phagosome or phagocytic vacuole (Figure 2–27); primary lysosomes then fuse with the membrane of the phagosome and empty their hydrolytic enzymes into the vacuole. Digestion follows, and the composite structure is now termed a secondary lysosome.

Figure 2-27
Current concepts of the functions of lysosomes. Synthesis occurs in the rough endoplasmic reticulum (RER), and the enzymes are packaged in the Golgi complex. Note the heterophagosomes, in which bacteria are being destroyed, and the autophagosomes, with RER and mitochondria in the process of digestion. Heterophagosomes and autophagosomes are secondary lysosomes. The result of their digestion can be excreted, but sometimes the secondary lysosome creates a residual body, containing remnants of undigested molecules. In some cells, such as osteoclasts, the lysosomal enzymes are secreted to the extracellular environment. Nu, nucleolus.

Secondary lysosomes are generally 0.2–2 micrometer in diameter and present a heterogeneous appearance in electron microscopes because of the wide variety of materials they may be digesting.

After digestion of the contents of the secondary lysosome, nutrients diffuse through the lysosomal-limiting membrane and enter the cytosol. Indigestible compounds are retained within the vacuoles, which are now called residual bodies (Figures 2–27 and 2–28). In some long-lived cells (eg, neurons, heart muscle), large quantities of residual bodies accumulate and are referred to as lipofuscin, or age pigment.

Figure 2-28
Section of a pancreatic acinar cell showing autophagosomes. Upper right: Two portions of the rough endoplasmic reticulum segregated by a membrane. Center: An autophagosome containing mitochondria (arrow) plus rough endoplasmic reticulum. Left: A residual body, with indigestible material. Arrowhead shows a cluster of coated vesicles.

Another function of lysosomes concerns the turnover of cytoplasmic organelles. Under certain conditions, a membrane may enclose organelles or portions of cytoplasm. Primary lysosomes fuse with this structure and initiate the lysis of the enclosed cytoplasm. The resulting secondary lysosomes are known as autophagosomes (Gr. autos, self, + phagein, to eat, + soma, body), indicating that their contents are intracellular in origin. Cytoplasmic digestion by autophagosomes is enhanced in secretory cells that have accumulated excess secretory product. The digested products of lysosomal hydrolysis are recycled by the cell to be reutilized by the cytoplasm.

Medical Apllication
In some cases, primary lysosomes release their contents extracellularly, and their enzymes act in the extracellular milieu. An example is the destruction of bone matrix by the collagenases synthesized and released by osteoclasts during normal bone tissue formation (see Chapter 8: Bone). Lysosomal enzymes acting in the extracellular milieu also play a significant role in the response to inflammation or injury. Several possible pathways relating to lysosome activities are schematically illustrated in Figure 2–27.

Lysosomes play an important role in the metabolism of several substances in the human body, and consequently many diseases have been ascribed to deficiencies of lysosomal enzymes. In metachromatic leukodystrophy, there is an intracellular accumulation of sulfated cerebrosides caused by lack of lysosomal sulfatases. In most of these diseases, a specific lysosomal enzyme is absent or inactive, and certain molecules (eg, glycogen, cerebrosides, gangliosides, sphingomyelin, glycosaminoglycans) are not digested. As a result, these substances accumulate in the cells, interfering with their normal functions. This diversity of affected cell types explains the variety of clinical symptoms observed in lysosomal diseases (Table 2–3).

Table 2–3. Examples of Diseases Caused by Lysosomal Enzyme Failure and Accumulation of Undigested Material in Different Cell Types.
Disease Faulty Enzyme Main Organs Affected
Hurler disease alfa-L-Iduronidase  Skeleton and nervous system
Sanfilippo syndrome A Heparan sulfate sulfamidase Skeleton and nervous system
Tay-Sachs Hexosaminidase-A Nervous system
Gaucher beta-D-Glycosidase  Liver and spleen
I-cell disease Phosphotransferase Skeleton and nervous system

I-cell disease (inclusion cell disease) is a rare inherited condition clinically characterized by defective physical growth and mental retardation and is due to a deficiency in a phosphorylating enzyme normally present in the Golgi complex. Lysosomal enzymes coming from the RER are not phosphorylated in the Golgi complex. Nonphosphorylated protein molecules are not separated to form lysosomes, instead following the main secretory pathway. The secreted lysosomal enzymes are present in the blood of patients with I-cell disease, whereas their lysosomes are empty. Cells of these patients show large inclusion granules that interfere with normal cellular metabolism.

References
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38 comments:

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Blog yang rame dengan pengunjung, sayang aku tak ngerti bahasanya :)

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@Nurcahyaku2.co.cc ini rame gara2 pake traffic sob...hahaha... :D

Ladida

lysosomes? lysosomes are found only in animals??

De Histology

@Ladida that's true... :D

Ladida

hohoo, it makes me confused, sometimes I think that lysosomes are found in plants :D

De Histology

@Ladida memang betul...tapi kalo yang ditumbuhan namanya beda "peroksisom"...fungsinya sama aja...sbg penghasil enzim... :)

Ladida

oooh, namanya aja yg beda, saya kira di tumbuhan ngga ada komponen sel kyk gini :D
di sekolah ngga ada atau saya yg kelewatan :P

YAng PEnting Share

ehmmm udah tau sih di SMA,tapi pas baca inggrisnya koq mumet ya??hahahaha

De Histology

gw juga bingung nih bos...kayaknya banyak banget dah organel2 yang ada di sel...di setiap buku aja versinya ada yang beda2... T-T

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