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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.”
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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.
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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
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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), ...