The bloodstream provides a readily available pool of amino acids, which can be taken up by all cells of the body to support the myriad of biochemical reactions that are essential for life. The transport of amino acids into the cytoplasm occurs via functionally and biochemically distinct amino acid transport systems that have been defined on the basis of their amino acid selectivities and physico-chemical properties. Each system presumably relates to a discrete putative membrane-bound transporter protein that resides within the cell membrane and functions to translocate the amino acid from the extracellular environment into the cytoplasm. Many of these transporters require sodium for maximal activity. The sodium-dependent model presented is consistent with "preferred random" kinetics, with sodium binding preferentially before the amino acid. The transporter acts as an enzyme that catalyzes the movement of its bound amino acid (and sodium) into the cell. In this review, the authors provide a conceptual view of the mechanism of carrier-mediated amino acid transport as well as an overview of the various models that can be used in the laboratory to study this process. In addition, the known agencies that accomplish transport and their regulation by nutrition, hormones, and other mediators of critical illness are discussed.

The transport of L-arginine by porcine pulmonary artery endothelial cells (PAECs) was characterized. Uptake of 50 microM L-arginine was time dependent and linear in the presence and absence of sodium, with approximately 70% of uptake occurring via a carrier-mediated Na(+)-independent process. Kinetic studies of saturable Na(+)-independent transport revealed two transport components: a high-affinity transporter [Michaelis constant (Km) = 304 +/- 23 microM, maximal transport velocity (Vmax) = 679 +/- 34 pmol.mg protein-1.30 s-1], and a low-affinity carrier (Km = 3.9 +/- 1.0 mM, Vmax = 2.8 +/- 0.7 nmol/mg protein-1.30 s-1). Saturable Na(+)-independent uptake of 50 microM L-arginine transport showed no significant variation in uptake between pH 6.0 and 8.0 and was blocked by the system y+ substrates L-arginine, L-homoarginine, L-lysine, and L-ornithine. Na(+)-dependent L-arginine transport occurred via a single high-affinity system (Km = 62 +/- 3 microM, Vmax = 211 +/- 24 pmol.mg protein-1.30 s-1) which was significantly inhibited by L-arginine, L-lysine, L-ornithine, L-leucine, L-alanine, L-cysteine, and L-glutamine, but not by 2-methylaminoisobutyric acid. Na(+)-dependent arginine uptake was pH and hormone insensitive, and lithium did not substitute effectively for sodium. These data are consistent with mediation of high-affinity arginine transport by PAECs via Na(+)-independent system y+ and Na(+)-dependent system BO,+.

Severe infection is characterized by a translocation of amino acids from the periphery to the liver, an event that is mediated in part by cytokines such as tumor necrosis factor-a (TNF). We investigated the activities of Na '-dependent transport systems A, ASC, and N in hepatic plasma membrane vesicles (HPMVs) prepared from rats treated with TNF in vivo. TNF did not alter sodium uptake but resulted in time-and dose-dependent fivefold and 50% maximal increases in system A and system N activity, respectively, in HPMVs secondary to an increase in the transport V n. Maximal increases in transport were observed 4 h after exposure to TNF and had returned to basal levels within 24 h. Similarly, system ASC activity was stimulated 80% in HPMVs from rats treated with TNF. Incubation of HPMVs from normal rats in vitro with TNF did not alter transport activity. Pretreatment of animals with the glucocorticoid receptor antagonist RU 38486 attenuated the TNFinduced enhancement in transport activity by 50%. The marked increase in Na'-dependent amino acid transport activity by TNF is mediated in part by the glucocorticoid hormones and represents an important mechanism underlying the accelerated hepatic amino acid uptake that occurs during critical illness. (J.