1.Lysosomal system - The primary lysosomes, budded from the Golgi complex, are bags of degradative enzymes. Over 50 different hydrolytic enzymes are contained in lysosomes, including proteases, nucleases, lipases, and carbohydrate-cleaving enzymes. The lysosomes play a number of important roles in cellular metabolism, as schematically depicted in Figure 28.42. In some cells, primary lysosomes migrate to the cell surface and release their contents into the exterior medium (path A, Figure 28.42). If primary lysosomes fuse with autophagic vesicles (formed when smooth endoplasmic reticulum engulfs organelles destined for destruction) (path B, Figure 28.42), the combined vesicle is called an autophagic lysosome. When primary lysosomes fuse with phagocytic vacuoles that have engulfed nutrient materials at the cell surface (path C, Figure 28.42), heterophagic lysosomes are created in which nutrients are digested and their amino acids, nucleotides, lipids, and other constituents are released into the cytosol.
2. Cytosolic Degradation System - Protease activity in the cytosol must be under rigid control, attacking only the proteins whose destruction is needed. Because general proteases would hydrolyze virtually all cytoplasmic proteins, cells must have a way to distinguish proteins to be attacked from those to be left alone.
Ubiquitin marking - The best-known cytoplasmic protein targeting system uses a protein called ubiquitin, a 76-residue polypeptide, found in virtually every eukaryotic cell. Marking and degradation proceeds as follows:
1. Ubiquitin's carboxyl group is activated by thiol coupling to an activating enzyme (Figure 28.43) in an ATP-dependent process.
2. The ubiquitin moieties are then transferred to a second enzyme (Figure 28.43, step 2).
3. The second enzyme attaches ubiquitin to
-amino groups of lysine residues on the fated protein (Figure 28.43, step 3).
4. Some ubiquinated proteins are simply marked for transloaction to specific cellular sites, and others are marked for reasons yet unknown, but most are marked for proteolytic digestion in particles called proteasomes.
Proteasomes - Both 20S and 26S proteasomes are known. Figure 28.44 shows the structure of the yeast 20S proteasome. Structurally, the proteasome shows remarkable similarity to the GroEL chaperonin (see here). Both are multitiered cylinders with 7-fold symmetry. Both can accept an unfolded polypeptide chain in their hollow interior. But whereas GroEL protects the polypeptide chain, the proteasome degrades it.