Dietary protein is a vital source of amino acids. Especially important dietary proteins are those containing the essential amino acids—amino acids that cannot be synthesized and must be acquired in the diet (Table 23.1). Proteins ingested in the diet are digested into amino acids or small peptides that can be absorbed by the intestine and transported in the blood. Another crucial source of amino acids is the degradation of cellular proteins.

Protein digestion begins in the stomach, where the acidic environment denatures proteins into random coils. Denatured proteins are more accessible as substrates for proteolysis than are native proteins. The primary proteolytic enzyme of the stomach is pepsin, a nonspecific protease that, remarkably, is maximally active at pH 2. Thus, pepsin can function in the highly acidic environment of the stomach that disables other proteins.

The partly digested proteins then move from the acidic environment of the stomach to the beginning of the small intestine. The low pH of the food as well as the polypeptide products of pepsin digestion stimulate the release of hormones that promote the secretion from the pancreas of sodium bicarbonate (NaHCO₃), which neutralizes the pH of the food, and a variety of pancreatic proteolytic enzymes. Recall that these enzymes are secreted as inactive zymogens that are then converted into active enzymes (Sections 9.1 and 10.4). The battery of enzymes displays a wide array of specificity, and so the substrates are degraded into free amino acids as well as di- and tripeptides. Digestion is further enhanced by proteolytic enzymes, such as aminopeptidase N, that are located in the plasma membrane of the intestinal cells. Aminopeptidases digest proteins from the amino-terminal end. Single amino acids, as well as di- and tripeptides, are transported into the intestinal cells.

At least seven different transporters exist, each specific to a different group of amino acids. A number of inherited disorders result from mutations in these transporters. For example, Hartnup disease, a rare disorder characterized by rashes, ataxia (lack of muscle control), delayed mental development, and diarrhea, results from a defect in the transporter for tryptophan and other nonpolar amino acids. The absorbed amino acids are subsequently released into the blood by a number of Na⁺–amino acid antiporters for use by other tissues (Figure 23.1).

Protein turnover —the degradation and resynthesis of proteins—takes place constantly in cells. Although some proteins are very stable, many proteins are short lived, particularly those that participate in metabolic regulation. These proteins can be quickly degraded to activate or shut down a signaling pathway. In addition, cells must eliminate damaged proteins. A significant proportion of newly synthesized protein molecules are defective because of errors in translation or misfolding. Even proteins that are normal when first synthesized may undergo oxidative damage or be altered in other ways with the passage of time. These proteins must be removed before they accumulate and aggregate. Indeed, a number of pathological conditions, such as certain forms of Parkinson disease and Huntington disease, are associated with protein aggregation.

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The half-lives of proteins range over several orders of magnitude. Ornithine decarboxylase, at approximately 11 minutes, has one of the shortest half-lives of any mammalian protein. This enzyme participates in the synthesis of polyamines, which are cellular cations essential for growth and differentiation. The life of hemoglobin, however, is limited only by the life of the red blood cell, and the lens protein crystallin is limited by the life of the organism.