Transport and Storage of Amino Acids
The normal concentration of amino acids in the blood is between 35 and 65 mg/dl. This is an average of about 2 mg/dl for each of the 20 amino acids, although some are present in far greater amounts than others. Because the amino acids are relatively strong acids, they exist in the blood principally in the ionized state, resulting from the removal of one hydrogen atom from the NH2 radical. They actually account for 2 to 3 milliequivalents of the negative ions in the blood. The precise distribu-tion of the different amino acids in the blood depends to some extent on the types of proteins eaten, but the concentrations of at least some individual amino acids are regulated by selective synthesis in the differ-ent cells.
Fate of Amino Acids Absorbed from the Gastrointestinal Tract.
The products of protein digestion and absorption in the gastrointestinal tract are almost entirely amino acids; only rarely are polypeptides or whole protein molecules absorbed from the digestive tract into the blood. Imme-diately after a meal, the amino acid concentration in a person’s blood rises, but the increase is usually only a few milligrams per deciliter, for two reasons: First, protein digestion and absorption are usually extended over 2 to 3 hours, which allows only small quantities of amino acids to be absorbed at a time. Second, after entering the blood, the excess amino acids are absorbed within 5 to 10 minutes by cells throughout the body, especially by the liver. Therefore, almost never do large concentrations of amino acids accumulate in the blood and tissue fluids. Nevertheless, the turnover rate of the amino acids is so rapid that many grams of proteins can be carried from one part of the body to another in the form of amino acids each hour.
Active Transport of Amino Acids into the Cells. The moleculesof all the amino acids are much too large to diffuse readily through the pores of the cell membranes. There-fore, significant quantities of amino acids can move either inward or outward through the membranes only by facilitated transport or active transport using carrier mechanisms. The nature of some of the carrier mecha-nisms is still poorly understood.
Renal Threshold for Amino Acids. In the kidneys, thedifferent amino acids can be actively reabsorbed through the proximal tubular epithelium, which removes them from the glomerular filtrate and returns them to the blood if they should filter into the renal tubules through the glomerular membranes. However, as is true of other active transport mechanisms in the renal tubules, there is an upper limit to the rate at which each type of amino acid can be transported. For this reason, when the concentration of a particular type of amino acid becomes too high in the plasma and glomerular filtrate, the excess that cannot be actively reabsorbed is lost into the urine.
Almost immediately after entry into tissue cells, amino acids combine with one another by peptide linkages, under the direction of the cell’s messenger RNA and ribosomal system, to form cellular proteins. Therefore, the concentration of free amino acids inside the cells usually remains low. Thus, storage of large quantities of free amino acids does not occur in the cells; instead, they are stored mainly in the form of actual proteins. But many of these intracellular proteins can be rapidly decomposed again into amino acids under the influence of intracellular lysosomal digestive enzymes; these amino acids can then be transported back out of the cell into the blood. Special exceptions to this reversal process are the proteins in the chromosomes of the nucleus and the structural proteins such as collagen and muscle contractile proteins; these proteins do not participate significantly in this reverse digestion and transport back out of the cells.
Some tissues of the body participate in the storage of amino acids to a greater extent than others. For instance, the liver, which is a large organ and has special systems for processing amino acids, can store large quantities of rapidly exchangeable proteins; this is also true to a lesser extent of the kidneys and the intestinal mucosa.
Release of Amino Acids from the Cells as a Means of Regulating Plasma Amino Acid Concentration. Whenever plasma aminoacid concentrations fall below normal levels, the required amino acids are transported out of the cells to replenish their supply in the plasma. In this way, the plasma concentration of each type of amino acid is main-tained at a reasonably constant value. Later, it is noted that some of the hormones secreted by the endocrine glands are able to alter the balance between tissue pro-teins and circulating amino acids. For instance, growth hormone and insulin increase the formation of tissue proteins, whereas adrenocortical glucocorticoid hor-mones increase the concentration of plasma amino acids.
Reversible Equilibrium Between the Proteins in Different Parts of the Body. Because cellular proteins in the liver (and, toa much less extent, in other tissues) can be synthesized rapidly from plasma amino acids, and because many of these proteins can be degraded and returned to the plasma almost as rapidly, there is constant interchange and equilibrium between the plasma amino acids and labile proteins in virtually all cells of the body. For instance, if any particular tissue requires proteins, it can synthesize new proteins from the amino acids of the blood; in turn, the blood amino acids are replenished by degradation of proteins from other cells of the body, especially from the liver cells. These effects are particu-larly noticeable in relation to protein synthesis in cancer cells. Cancer cells are often prolific users of amino acids; therefore, the proteins of the other cells can become markedly depleted.
Upper Limit for the Storage of Proteins. Each particular typeof cell has an upper limit with regard to the amount of proteins it can store. After all the cells have reached their limits, the excess amino acids still in the circulation are degraded into other products and used for energy, as discussed subsequently, or they are converted to fat or glycogen and stored in these forms.