Uptake and Metabolism of L-Proline by Human Kidney Cortex

Abstract

A specific aminoaciduria involving glycine and the imino acids, proline and hydroxyproline, has been found in patients with defective proline catabolism (hyperprolinemia I and II) and in patients with renal imino-glycinuria, a selective defect in tubular reabsorption. To further elucidate the transport mechanisms of these amino acids, we have studied the uptake and metabolism of ¹⁴ labeled L-proline in cortex slices of ‘normal’ human kidney obtained from surgical specimens. Metabolism of proline was considerable, with 80% or more of the calculated uptake recoverable as ₁₄CO₂ during a short incubation over a wide substrate range (0.065 to 50 mM/L). Further, only 33–50% of tissue radioactivity was recovered as proline, proportion increasing with increasing media concentration. Of the remaining tissue label, the majority was recovered as glutamic acid with proportions increasing with time to 75% at steady state conditions. Formation of glutamic acid was maekedly inhibited by anerobiasis. Uptake of proline demonstrated saturable kinetics, with two apparently distinct concentration dependent systems—high capacity, low affinity at high proline concentrations and low capacity, high affinity at low concentrations. Kinetics of oxidation followed an almost identical pattern. Glycine was a non-competitive inhibitor of proline uptake in the ‘high’ system and competitive in the ‘low’; however ¹⁴CO₂ production was unaltered by glycine inhibition. Although kinetics of proline uptake could be determined in human kidney cortex, the data indicates that extensive metabolism precludes formation of a true concentration gradient and emphasizes a possible role of proline catabolism in the process of tubular reabsorption.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD