Recent advances in mammalian amino acid transport.

Abstract

During the last four decades, mammalian amino acid transport systems have been described at the cellular level through general properties such as ion-dependence, kinetics, substrate specificity, regulation of activity, and numerous other characteristics. These studies have allowed the definition of multiple transport systems for neutral, anionic, and cationic amino acids. Each system is distinct but exhibits overlapping substrate specificity. Direct measurement of transport has permitted a wealth of information to be accumulated regarding the regulation of overall activity, but the underlying molecular mechanisms have not been investigated because of a lack of the appropriate tools. Recent research designed to obtain these tools has proven fruitful, and the field of amino acid transport clearly is entering a new era. In the immediate future, transporter properties such as hormonal regulation, adaptive control, ion-dependence, and trans-effects will be studied at the molecular level by assaying mRNA or protein content and by analyzing results obtained with altered protein structures following site-directed mutagenesis. Identification of specific proteins associated with activities already well described will provide answers to heretofore untestable questions. For example, is Na(+)-independent transport mediated by the same proteins that mediate Na(+)-dependent uptake except that their function in this mode does not require sodium binding? What is the protein composition of amino acid transporters? As discussed above, emerging evidence suggests that transporter proteins have different molecular structure, 12 versus 1 transmembrane domains, or that they exist as heterodimers or heterotetramers. Identification of certain transporter proteins and cloning of the respective genes also will provide valuable information about a number of inheritable diseases that are thought to be caused by defects in transporter synthesis or function. The opportunity to ask these questions will certainly generate renewed interest in the field of amino acid transport and lead to exciting advances in our knowledge.