Acidic amino acid transport in animal cells and tissues

Abstract

1. 1. The occurrence and characterization of acidic amino acid transport in the plasma membrane of a variety of cells and tissues of a number of organisms is reviewed. 2. 2. Several cell types, especially in brain, possess both high- and low-affinity transport systems for acidic amino acids. 3. 3. High-affinity systems in brain may function to remove neurotransmitter amino acid from the extracellular environment. 4. 4. Many cell systems for acidic amino acid transport are energized by an inwardly directed Na + gradient. Moreover, certain cell types, such as rat brain neurons, human placental trophoblast and rabbit and rat kidney cortex epithelium, respond to an outwardly directed K + gradient as an additional source of energization. This simultaneous action may account for the high accumulation ratios seen with acidic amino acids. 5. 5. Rabbit kidney has been found to have a glutamate—H + co-transport system which is subject to stimulation by protons in the medium. 6. 6. Acidic amino acid transport in rat brain neurons occurs with a stoichiometric coupling of 1 mol of amino acid to 2 mol of Na +. For rabbit intestine, one Na + is predicted to migrate for each mol of amino acid 7. 7. Uptake in rat kidney cortex and in high-K + dog erythrocytes is electrogenic. However, uptake in rabbit and newt kidney and in rat and rabbit intestine is electroneutral. 8. 8. Na +-independent acidic amino acid transport systems have been described in the mouse lymphocyte, the human fibroblast, the mouse Ehrlich cell and in rat hepatoma cells. 9. 9. In a number of cell systems, d-acidic amino acids have substantial affinity for transport; d-glutamate, in a number of systems, however, appears to have little reactivity. 10. 10. Acidic amino acid transport in some cell systems appears to occur via the “classical” routes (Christensen, Adv. Enzymol. Relat. Areas Mol. Biol. 49, 41–101, 1979). For example, uptake in the Ehrlich cell is partitioned between the Na +-dependent A system (which transports a wide spectrum of neutral amino acids), the Na +-dependent ASC system (which transports alanine, serine, threonine, homoserine, etc.), and the Na +-independent L system (which shows reactivity centering around neutral amino acids such as leucine and phenylalanine). Also, a minor component of uptake in mouse lymphocytes occurs by a route resembling the A system. 11. 11. Human fibroblasts possess a Na +-independent adaptive transport system for cystine and glutamate that is enhanced in activity by cystine starvation. This system is apparently regulated by intracellular glutathione, which inhibits carrier synthesis, as well as by electrophilic agents such as diethyl maleate which increase carrier synthesis. It appears to function in protecting cells against electrophilic agents. 12. 12. Gamma-glutamyl transpeptidase (pig kidney cortex) catalyzes glutamate transport when this enzyme is incorporated into phospholipid vesicles. 13. 13. Transintegumentary uptake in a number of parasitic organisms may play a role in reabsorption of acidic amino acids lost from surface cells by diffusion.