Comparative study of the uptake of L-cysteine and L-cystine in the renal proximal tubule.

1. The transport mechanisms of L-cysteine and L-cystine by luminal membrane vesicles isolated from either the proximal convoluted part (pars convoluta) or the proximal straight part (pars recta) of rabbit proximal tubuli were examined. 2. The uptake of L-cysteine in pars convoluta is characterized by a single sodium-dependent transport system (Km = 0.58 mM), whereas the sodiumdependent influx of L-cysteine in pars recta proceeds via transport systems with different affinities (Km1 = 0.03 mM, Km2 = 5.84 mM). An H(+)-gradient enhanced the uptake of L-cysteine in pars recta and only in the presence of a Na(+)-gradient. 3. The presence of a Na(+) gradient stimulated the influx of L-cystine in both parts of the nephron, but to a lesser extent than for L-cysteine. In addition a considerable amount of binding of L-cystine to membrane vesicles was observed in both pars convoluta and pars recta. 4. Stoichiometric studies indicated a coupling ratio of 1 Na(+): 1 amino acid for the transport components involved in the uptake of L-cysteine and L-cystine along the proximal tubule. 5. Competition experiments demonstrated that neutralα-amino acids inhibited the influx of L-cysteine in the proximal tubule. Basic and acidic amino acids had no effect on uptake of L-cysteine in pars convoluta, whereas a slight inhibitory effect of L-lysine and L-arginine was noted in pars recta. 6. Both basic and neutral amino acids, but not L-glutamate inhibited the uptake of L-cystine in pars convoluta. This was in general also the case in pars recta. However, addition of L-proline did not influenced the uptake of L-cystine, and L-phenylalanine, L-asparagine, L-glutamine, L-leucine and L-methionine only inhibited at a high concentration (5 mM).