The total amount of protein in the body remains constant in healthy adults because the rate of protein synthesis is sufficient to replace the degraded protein. This process, known as protein turnover, involves the hydrolysis and resynthesis of 300-400 g of body protein per day. The rate of protein turnover varies for different proteins. Short-lived proteins, including regulatory and misfolded proteins, are rapidly degraded, with half-lives measured in minutes or hours. Long-lived proteins, which make up the majority of cellular proteins, have half-lives ranging from days to weeks. Structural proteins, such as collagen, are metabolically stable and have half-lives measured in months or years.

Protein degradation is carried out by two major enzyme systems: the ATP-dependent ubiquitin-proteasome system in the cytosol and the ATP-independent degradative enzyme system in the lysosomes. Proteasomes selectively degrade damaged or short-lived proteins, while lysosomes use acid hydrolases to nonselectively degrade intracellular and extracellular proteins. The ubiquitin-proteasome system involves the covalent attachment of ubiquitin to the target substrate through a three-step process. Ubiquitin molecules are added consecutively to generate a polyubiquitin chain, which is recognized by the proteasome. The proteasome unfolds, deubiquitinates, and cuts the target protein into fragments that are further degraded by cytosolic proteases to amino acids. The ubiquitin is recycled. It is important to note that the selective degradation of proteins by the ubiquitin-proteasome complex requires ATP hydrolysis.

Protein degradation is not random but influenced by structural aspects of the protein that serve as degradation signals. These signals are recognized and bound by E3 proteins. The half-life of a protein is also influenced by the N-terminal residue, known as the N-end rule, which can range from minutes to hours. Certain amino acids, such as arginine and posttranslationally modified amino acids, destabilize proteins, while others like serine stabilize them. Proteins rich in sequences containing proline, glutamate, serine, and threonine (PEST sequences) are rapidly ubiquitinated and degraded, resulting in short half-lives.

Now let's move on to the process of dietary protein digestion.
Rate: In healthy adults, the total amount of protein in the body remains constant because the rate of protein synthesis is just sufficient to replace the protein that is degraded. This process, called protein turnover, leads to the hydrolysis and resynthesis of 300–400 g of body protein each day. The rate of protein turnover varies widely for individual proteins. Short-lived proteins (for example, many regulatory proteins and misfolded proteins) are rapidly degraded, having half-lives measured in minutes or hours. Long-lived proteins, with half-lives of days to weeks, constitute the majority of proteins in the cell. Structural proteins, such as collagen, are metabolically stable and have half-lives measured in months or years.
2.
Protein degradation: There are two major enzyme systems responsible for degrading proteins: the ATP-dependent ubiquitin (Ub)–proteasome system of the cytosol and the ATP-independent degradative enzyme system of the lysosomes. Proteasomes selectively degrade damaged or short-lived proteins. Lysosomes use acid hydrolases (see p. 162) to nonselectively degrade intracellular proteins (autophagy) and extracellular proteins (heterophagy), such as plasma proteins, that are taken into the cell by endocytosis.
a. Ubiquitin–proteasome system: Proteins selected for degradation by the cytosolic ubiquitin–proteasome system are first modified by the covalent attachment of Ub, a small, globular, nonenzymic protein that is highly conserved across eukaryotic species. Ubiquitination of the target substrate occurs through isopeptide linkage of the α-carboxyl group of the C-terminal glycine of Ub to the ε-amino group of a lysine in the protein substrate by a three-step, enzyme-catalyzed, ATP-dependent process. [Note: Enzyme 1 (E1, an activating enzyme) activates Ub, which is then transferred to E2 (a conjugating enzyme). E3 (a ligase) identifies the protein to be degraded and interacts with E2-Ub. There are many more E3 proteins than there are E1 or E2.] The consecutive addition of four or more Ub molecules to the target protein generates a polyubiquitin chain. Proteins tagged with Ub chains are recognized by a large, barrel-shaped, macromolecular, proteolytic complex called a proteasome (Fig. 19.3). The proteasome unfolds, deubiquitinates, and cuts the target protein into fragments that are then further degraded by cytosolic proteases to amino acids, which enter the amino acid pool. The Ub is recycled. It is noteworthy that the selective degradation of proteins by the ubiquitin–proteosome complex (unlike simple hydrolysis by proteolytic enzymes) requires ATP hydrolysis.
b. Degradation signals: Because proteins have different half-lives, it is clear that protein degradation cannot be random but, rather, is influenced by some structural aspect of the protein that serves as a degradation signal, which is recognized and bound by an E3. The half-life of a protein is also influenced by the amino (N)-terminal residue, the so-called N-end rule, and ranges from minutes to hours. Destabilizing N-terminal amino acids include arginine and posttranslationally modified amino acids such as acetylated alanine. In contrast, serine is a stabilizing amino acid. Additionally, proteins rich in sequences containing proline, glutamate, serine, and threonine (called PEST sequences after the one-letter designations for these amino acids) are rapidly ubiquitinated and degraded and, therefore, have short half-lives.
III. DIETARY PROTEIN DIGESTION