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Biochemically Characterized Amino Acid and Peptide Transport Systems

Amino acid transporters

The study of how cells absorb -amino acid nitrogen historically has followed the study of free or peptide-bound amino acids. The work of Halvor Christensen and colleagues has resulted in the characterization of a number of separate amino acid transport systems in epithelial and non-epithelial cells.

These transport activities typically are categorized according to their required energy sources, substrate specificities and kinetics of absorption. The characterization of amino acid transport processes has resulted in the paradigm that translocation of free amino acids across cellular membranes occurs by multiple transport activities, often with overlapping substrate specificities for amino acids of the same and/or different class.

For example, lysine and leucine are each recognized by at least four biochemically distinct amino acid transport systems, with three of these transport systems recognizing both substrates. Amino acid transport systems display varying degrees of substrate specificities

system IMINO, which is specific for proline, to system Bo,+, which accepts most dipolar and cationic amino acids. Free -amino acid transporters, however, do not recognize – amino acids (e.g. taurine). Recognition of amino acids by transport proteins is thought to be dependent on the group (for proline) and a carboxyl group, with the size, charge and/or configuration of the side chains acting as important determinants for substrate transport

It is clear from reported free amino acid transport activities of mammalian fibroblasts, skeletal muscle, hepatocytes, enterocytes, placental trophoblasts and pancreatic acinar cells that the expression of transporter activities differs among types of cells and between the membranes of cells. It is also apparent that several transport activities are expressed in most types of cells.

Part of this heterogeneity in amino acid absorption capacity appears to be associated with substrate supply. For example, only the intestinal lumen-facing brush border membranes of enterocytes and the bile-facing canalicular membranes of hepatocytes do not express systems A and ASC and, instead, rely on systems B and Bo,+ to absorb dipolar amino acids.

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Additionally, the expression of system Bo,+ confers an added capacity for cationic amino acid transport, as compared with other cells and membranes which only express system y+. Interestingly, enterocytes also express system IMINO for the absorption of proline in the apical membrane, which is readily transported by system A in the basolateral membrane and in cells other than enterocytes.

System L, a predominant Na+- independent transporter of large hydrophobic dipolar amino acids, also is not expressed in the apical membrane of enterocytes, but is in the basolateral membranes

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