Abstract
ADEQUATE membrane transport of L-cysteine is necessary for red blood cell (RBC) survival, as this amino acid is essential for glutathione (GSH) synthesis and thus cell protection against oxidative damage. Thus, in sheep a genetically controlled L-cysteine transport defect leads to a reduced intracellular GSH concentration and shortened cell lifespan1–4. Human RBCs do not have the same amino acid transport system as sheep red blood cells (SRBC)5, the principal component being a high capacity, medium affinity system with a specificity broadly directed towards large neutral amino acids, the L-system of Christensen6. L-cysteine and its analogue L-α-amino-n-buty-rate are carried by the L-system in human RBCs, but with a low affinity7. Most experiments on amino acid transport in RBCs, particularly involving the L-system, have revealed substrate affinities with apparent Km values in the millimolar range, much higher than the physiological plasma levels of most amino acids. We have now investigated L-cysteine uptake in human RBCs over the concentration range 1–50 µm, as human plasma levels are around 20 µM8,9. As the early work of Yunis and Arimura10 has shown that glycine and L-alanine transport are partially Na-dependent, we have also investigated the effects of removing external Na on L-cysteine transport. We report here that human RBCs transport L-cysteine by a previously unidentified high affinity, low capacity, Na-dependent uptake mechanism. This system has a uniquely high affinity for its substrate and is the first Na-dependent transport mechanism to be kinetically characterised in mammalian erythrocytes. At physiological substrate concentrations it accounts for approximately half of the L-cysteine uptake into the cell.
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YOUNG, J., WOLOWYK, M., JONES, S. et al. Sodium-dependent cysteine transport in human red blood cells. Nature 279, 800–802 (1979). https://doi.org/10.1038/279800a0
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DOI: https://doi.org/10.1038/279800a0
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