Interaction of proline, 5-oxoproline, and pipecolic acid for renal transport in the rabbit.

The transport of proline, 5-oxoproline, and pipecolic acid and their mutual interactions during transport were studied in purified brush-border membrane vesicles from rabbit renal cortex. The presence of a Na’ gradient stimulated the transport of these compounds. 5-Oxoproline was transported by a single system with an apparent K,,, of 20.4 mM. Many neutral amino acids and 6-piperidone-2-carboxylic acid, an analog of &oxoproline, inhibited its transport and the inhibition was competitive. Proline was transported by two different systems. The high affinity system was predominantly responsible for proline transport at physiological concentrations of proline and it had a K,,, of 0.23 mM and a V,,, of 0.17 nmol/mg of protein/30 s. The second component may correspond to the low affinity system observed in the human kidney. Proline transport a t a wide range of concentrations was competitively inhibited by pipecolic acid, suggesting interaction of pipecolic acid with both transport systems of proline. The Ki for pipecolic acid was 0.27 mM. Hydroxyproline, 5oxoproline, 6-piperidone-2-carboxylic acid, and many neutral amino acids inhibited proline transport by the high affinity system, whereas glycine had no noticeable effect. Pipecolic acid transport was completely inhibited by proline and hydroxyproline, and moderate to significant inhibition was observed with 5-oxoproline and neutral amino acids. It is concluded that proline and pipecolic acid share a common transport system@) in the rabbit kidney. A strong interaction between 5-oxoproline and many neutral amino acids indicates that this cyclic lactam may compete with neutral amino acids for the same transport carrier. However, it is equally possible that the mutual inhibition is due to competition between 5-oxoproline and the neutral amino acids for the Na’ gradient.