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Epithelial cells in such places as renal tubules and intestinal mucosa utilize several different transport systems that move amino acids through the luminal (apical) and the antiluminal (basolateral) membranes of the cell in functional cooperation, utilizing sodium-dependent symporters, proton-motive forces, and concentration gradients of other amino acids. Each system prefers groups of amino acids with certain physicochemical properties, but most individual amino acids can use more than one transporter. The transport activities have been classified in five main groups: (1) the “basic system” for cystine and the structurally related dibasic cationic amino acids lysine, arginine, and ornithine; (2) the “neutral system” for neutral amino acids; (3) the “acidic system” for glutamate and aspartate; (4) the “iminoglycine system” for proline, hydroxyproline, and glycine; and (5) the “beta-amino acid system.”

Within the basic system, cystine, lysine, arginine, and ornithine are transported from the intestinal or renal tubular lumen into the epithelial cells by a luminal transporter in exchange for neutral amino acids. The dibasic amino acids are then transported from the epithelial cell into the tissues by an antiluminal (basolateral) dibasic amino acid transporter in exchange for neutral amino acids and sodium. Both these transporters are heteromers of a heavy subunit (N-glycosylated type 2 membrane glycoprotein) and a light subunit (nonglycosylated polytopic membrane protein) linked by a disulfide bridge.

The neutral transporter system is expressed only at the luminal border of the epithelial cells. It transports alanine, asparagine, citrulline, glutamine, histidine, isoleucine, leucine, phenylalanine, serine, threonine, tryptophan, tyrosine, and valine into the epithelial cells (Fig. 143-1).1,2As the number of molecularly identified amino acid transporters increases, the nomenclature based on gene homology in solute carrier families (SLC) will improve the accuracy of the classification.1,3

Figure 143-1.

Simplified schematic representation of amino acid transport in proximal tubular epithelial cell. Transport systems for negatively charged dicarboxylic amino acids (AA-), imino acids, (glycine, proline, and hydroxyproline); neutral amino acids (AA); and cystine and positively charged dibasic amino acids (AA+) are shown. The special transporters, some of which are formed of light and heavy subunits, act on the luminal and basolateral membranes of the epithelial cell. In man, the transporters for neutral amino acids (B0AT1/SLC6A19), for cationic dibasic amino acids and cystine at the luminal surface (formed by subunits b0,+AT/SLC7A9 and rBAT/SLC3A1), and for dibasic amino acids at the basolateral surface (formed by subunits +LAT1/SLC7A7 and 4F2hc/SLC3A2) have been characterized at the gene and molecular level. The subunits that carry mutations that cause Hartnup disorder, cystinuria and lysinuric protein intolerance, are shown in red.

The principal selective aminoacidurias, cystinuria, lysinuric protein intolerance, and Hartnup disorder are caused by defects of the luminal cystine/dibasic amino acid transporter (encoded by the genes SLC3A1 and SLC7A9), the antiluminal or basolateral dibasic amino acid transporter (encoded by SLC7A7), ...

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