The transport of neutral amino acids in mammalian cells is broadly described as occurring through two parallel pathways, one Na?+?-dependent and the other Na?+?-independent. The """"""""Na?+?-gradient hypothesis"""""""" proposes that the electrochemical potential gradient for Na?+? serves as the sole energy source for driving accumulation of amino acids by the Na?+?-dependent system. The source of energy for uptake of Na?+?-independent amino acids is not known. This research is based on two hypotheses: (1) the cell membrane potential plays an essential role in the provision of nutrients necessary for cellular metabolism and (2) a single transport pathway serves for the cellular uptake of both Na?+?-dependent and Na?+?-independent neutral amino acids. We have determined in the Ehrlich ascites tumor cell: (1) the coupling stoichiometry of Na?+?-amino acid co-transport is consistent with the transport of one Na?+?/amino acid; (2) the Na?+? electrochemical potential gradient is sufficient to provide the energy necessary for amino acid accumulation; (3) the cell membrane is repolarized by active Na?+? extrusion following addition of amino acids; and (4) H?+? may substitute for Na?+? as a co-substrate suggesting that the same transport system serves for Na?+?-dependent and Na?+?-independent amino acids. Ongoing studies are directed toward the evaluation of proton gradients as sources of energy for Na?+?-independent amino acid transport and the interactions of Na?+?- and H?+?-dependent co-transport. We anticipate that this investigation will lead to a more complete understanding of the energetics involved in meeting the cell's nutritional requirements. (A)
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| Smith, T C; Levinson, C (1989) Quinine inhibits multiple Na+ and K+ transport mechanisms in Ehrlich ascites tumor cells. Biochim Biophys Acta 978:169-75 |
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| Dawson, W D; Smith, T C (1986) Intracellular Na+, K+ and Cl- activities in Ehrlich ascites tumor cells. Biochim Biophys Acta 860:293-300 |
