Lysosomes and Peroxisomes

Physiologists often view lysosomes as the digestive system of the cell. These small, membrane-enclosed sacs contain powerful hydrolytic enzymes. These enzymes can break down and recycle worn-out cell parts. They also break down foreign substances such as bacteria taken into the cell. All of the lysosomal enzymes are acid hydrolases, which means that they require an acid environment. The lysosomes provide this environment by maintaining a pH of approximately 5 in their interior. The pH of the cyto­plasm, which is approximately 7.2, serves to protect other cellular structures from this acidity. Like many other or-ganelles, lysosomes have a unique surrounding membrane that can be pinched off to form vesicles that transport materials throughout the cytoplasm.

Endoplasmic reticulum (ER)

Transfer vesicles

Secretory granules

Synthesis of lysosomal enzymes occurs in the rough ER. After transport to and uptake by the Golgi apparatus, the Golgi biochemically modifies and packages these ma­terials as lysosomes. Unlike other organelles, the sizes and functions of lysosomes vary considerably. This diversity is determined by the type of enzyme packaged in the lyso-some by the Golgi complex. Primary lysosomes contain hydrolytic enzymes that have not yet entered the digestive process. They become secondary lysosomes after activation of their enzymes has occurred and the chemical degradation process has begun. Primary lysosomes can form secondary lysosomes in one of two ways: heterophagy or autophagy (Fig. 4-5). Heterophagocytosis refers to the uptake of material from outside the cell. An infolding of the cell membrane takes external materials into the cell to form a surround-

Golgi apparatus

IGURE 4-4 Hormone synthesis and secretion. In hormone secre­tion, the hormone is synthesized by the ribosomes attached to the rough endoplasmic reticulum. It moves from the rough ER to the Golgi complex, where it is stored in the form of secretory granules. These leave the Golgi complex and are stored within the cytoplasm until released from the cell in response to an appropriate signal.

 

IGURE 4-5 The process of autophagy and heterophagy, showing the primary and secondary lysosomes, residual bodies, extrusion of residual body contents from the cell, and lipofuscin-containing residual bodies.

ing phagocytic vesicle or phagosome. Primary lysosomes then fuse with phagosomes to form secondary lysosomes. Heterophagocytosis is most common in phagocytic white blood cells such as neutrophils and macrophages. Au-tophagocytosis involves the removal of damaged cellular or­ganelles, such as mitochondria or ER, which the lysosomes must remove if the cell's normal function is to continue. Autophagocytosis is most pronounced in cells undergoing atrophy.

Although enzymes in the secondary lysosomes can break down most proteins, carbohydrates, and lipids to their basic constituents, some materials remain undigested. These undigested materials may remain in the cytoplasm as residual bodies or are extruded from the cell by exocyto­sis. In some long-lived cells, such as neurons and heart muscle cells, large quantities of residual bodies accumulate as lipofuscin granules or age pigment. Other indigestible pigments, such as inhaled carbon particles and tattoo pig­ments, also accumulate and may persist in residual bodies for decades.

Lysosomes play an important role in the normal me­tabolism of certain substances in the body. In some inher­ited diseases known as lysosomal storage diseases, a specific lysosomal enzyme is absent or inactive, in which case the di­gestion of certain cellular substances (e.g., glucocerebrosides, gangliosides, sphingomyelin) does not occur. As a result, these substances accumulate in the cell. In Tay-Sachs dis­ease, an autosomal recessive disorder, hexosaminidase A, which is the lysosomal enzyme needed for degrading the GM₂ ganglioside found in nerve cell membranes, is defi­cient. Although GM₂ ganglioside accumulates in many tis­sues, such as the heart, liver, and spleen, its accumulation in the nervous system and retina of the eye causes the most damage (see Chapter 7).

Smaller than lysosomes, spherical membrane-bound organelles called peroxisomes contain a special enzyme that

degrades peroxides (e.g., hydrogen peroxide). Peroxisomes function in the control of free radicals (see Chapter 5). Un­less degraded, these highly unstable chemical compounds would otherwise damage other cytoplasmic molecules. For example, catalase degrades toxic hydrogen peroxide mol­ecules to water. Peroxisomes also contain the enzymes needed for breaking down very-long-chain fatty acids, which mitochondrial enzymes ineffectively degrade. In liver cells, peroxisomal enzymes are involved in the for­mation of the bile acids. In a genetic disease called adreno-leukodystrophy, the most common disorder of peroxisomes, a buildup of long-chain fatty acids occurs in the nervous system and adrenal gland. The disorder, which is rapidly progressive and fatal, results in dementia and adrenal in­sufficiency because of the accumulation of the fatty acids.