The transformation and fate of food proteins from their ingestion to the elimination of their excretion products. Proteins are of exceptional importance to organisms because they are the chief constituents, aside from water, of all the soft tissue of the body. Special proteins have unique roles as structural and functional elements of cells and tissues. Examples are keratin of skin, collagen of tendons, actin and myosin of muscle, the blood proteins, enzymes in all tissues, and protein hormones of the hypophysis. See also Blood; Enzyme; Hormone; Muscle.
Isotopic labeling experiments have established that body proteins are in a dynamic state, constantly being broken down and replaced. This is a rapid process in organs active in metabolism, such as liver, kidney, intestinal mucosa, and pancreas, much slower in skeletal muscle, and extremely slow in connective tissue elements and skin.
Protein is digested to amino acids in the gastrointestinal tract. These are absorbed and distributed among the different tissues, where they form a series of amino acid pools that are kept equilibrated with each other through the medium of the circulating blood. The needs for protein synthesis of the different organs are supplied from these pools. Excess amino acids in the tissue pools lose their nitrogen by a combination of transamination and deamination. The nitrogen is largely converted to urea and excreted in the urine. The residual carbon products are then further metabolized by pathways common to the other major foodstuffs—carbohydrates and fats. See also Carbohydrate; Lipid.
Ingestion of protein is needed primarily to supply amino acids for the formation of new and depleted body protein and as a source of various other body constituents derived from the amino acids. The amino acids of proteins fall into two nutritional categories: essential or indispensable, and nonessential or dispensable. For a number of amino acids, the category to which they belong changes between the periods of body growth and adulthood and changes also in different animal species. Eight essential amino acids are needed for maintenance of nitrogen equilibrium in healthy young men. The remaining amino acids can be formed in the body from other materials. See also Amino acids.
Protein digestion occurs to a limited extent in the stomach and is completed in the duodenum of the small intestine. The main proteolytic enzyme of the stomach is pepsin, which is secreted in an inactive form, pepsinogen. Its transformation to the active pepsin, initiated by the acidity of the gastric juice, involves liberation of a portion of the pepsinogen molecule as a peptide. Pepsin preferentially hydrolyzes peptide bonds containing an aromatic amino acid, and it requires an acid medium to function. See also Digestive system; Pepsin.
The acid chyme is discharged from the stomach, containing partially degraded proteins, into a slightly alkaline fluid in the small intestine. This fluid is composed of pancreatic juice and succus entericus, the intestinal secretion. The pancreas secretes three known proteinases, trypsin, chymotrypsin, and carboxypeptidase. All three are secreted as inactive zymogens. Activation starts with the transformation of the inactive trypsinogen into the active trypsin. Trypsin, in turn, activates chymotrypsin and carboxypeptidase. See also Peptide.
Trypsin and chymotrypsin are endopeptidases; that is, they cleave internal peptide bonds. The so-called peptidases are exopeptidases; they cleave terminal peptide bonds. Trypsin has a predilection for those containing the basic amino acid residues of lysine and arginine. These two proteinases perform the major share in hydrolyzing proteins to small peptides. Digestion to amino acids is completed by the exopeptidases. Carboxypeptidase acts on peptides from the free carboxyl end; aminopeptidases from the free amino end. Other peptidases act on di- or tripeptides, or peptides containing such special amino acids as proline.
The amino acid digestion products of the proteins are absorbed by the small intestine as rapidly as they are liberated. The absorbed amino acids are carried by the portal blood system to the liver, from which they are distributed to the rest of the body. Small amounts of the peptides formed during digestion escape further hydrolysis and may also enter the circulation from the intestine. This is shown by a rise in the peptide nitrogen in the blood.
The unabsorbed food residue in the small intestine is passed into the cecum, then the colon, and finally is eliminated as feces.
The absorbed amino acids that escape decomposition become part of the amino acid pools of the body. From these amino acids, new tissue proteins are synthesized to meet body needs. The rate of tissue replacement varies greatly for different tissues. In humans, it has been estimated that the average half-life of the total body protein is 80 days; that of lung, brain, bone, skin, and most muscle combined is 158 days; while that of liver and serum proteins combined is only 10 days.
The major organ of plasma protein synthesis is the liver. It forms all of the plasma albumin and fibrinogen and a considerable proportion of the globulins. (A portion of the total plasma globulin is synthesized in other tissues containing reticuloendothelial cells. The hormones and enzymes present in blood plasma are derived in the main from nonhepatic sources.) See also Albumin; Fibrinogen; Liver.
The plasma proteins have numerous important physiological functions. The albumin is the major factor in the regulation of the blood volume through its osmotic action, which counteracts the fluid expulsion effect of the hydrostatic pressure resulting from the contractions of the heart. Fibrinogen is one component of a sequential process essential for coagulation of the blood. Other plasma components include the blood platelets and prothrombin. The globulins include fractions that are carriers of phospholipids and sterols and certain essential metal ions, iron, and copper. Other fractions, chiefly γ-globulin, contain the antibodies that are the defenses against numerous diseases.
Synthesis and utilization of the plasma proteins is a rapid process. There is a complete turnover of the major plasma proteins in a period of a few days. The difference from normal in the turnover times in a variety of diseases provides an insight into the nature of the disease processes.
