Given the central role of the placenta in nutrient transport to the fetus, one might propose that maternal nutrition would have a regulatory effect on this nutrient delivery. We have examined the effect of a low-protein adequate-calorie diet on specific amino acid transport processes by the rat placenta. Maternal weight, fetal weight, and placental weight were all significantly reduced in dams fed a low-protein (5% casein), isocaloric diet when compared with dams pair-fed a control (20% casein) diet. Even though maternal serum amino acid levels were maintained in the low-protein animals, fetomaternal serum amino acid ratios were significantly reduced, suggesting a reduction in nutrient transfer to the fetus. Apical and basal membrane vesicles were isolated from the placental trophoblast and were used to examine the amino acid transport capacity of both maternal-facing and fetal-facing membranes, respectively. Na+-dependent neutral amino acid transport mediated by system A was decreased in both membrane preparations, while transport mediated by system ASC was unaffected. The Na+-dependent anionic amino acid uptake by system X(-)AG (EAAC1) was reduced on the basal membrane, while the Na+-independent component was similar between the low-protein and control diet-fed dams. Cationic amino acid uptake was also reduced on both membrane surfaces. A decreased steady-state mRNA content for EAAC1 and CAT1 (system y+) suggests that reduced synthesis of the transporter proteins is responsible for the decrease in transport activity. Taken together, these data support the hypothesis that maternal protein malnutrition affects nutrient delivery to the fetus by downregulation of specific amino acid transport proteins.

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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.