Evidence for distinct pathways in rabbit renal brush-border membrane vesicles for the transport of unsubstituted and alpha-hydroxysubstituted aliphatic monocarboxylic acids.

We evaluated the effects of unsubstituted and hydroxymonocarboxylic acids on the kinetics of Na+-dependent L-lactate uptake in brush-border membrane vesicles prepared from the whole cortex of rabbit kidney. Acetate, propionate, and butyrate reversibly inhibited Na+-dependent L-lactate influx with [I]0.5 values of 5.5, 0.50, and 0.25 mM, respectively. Dixon plots (1/V versus acetate, propionate, and butyrate) were curved concavely downward, indicating partial inhibition. The Hill coefficients were approximately 1.0, suggesting that these anions interact at a single site on the Na+-L-lactate cotransporter. Acetate and the two other unsubstituted short-chain fatty acids tested decreased Na+-dependent L-lactate influx by increasing Km and decreasing Vmax, indicating mixed-type inhibition. In contrast, Na+-dependent L-lactate uptake was competitively inhibited by alpha-hydroxybutyrate and D-lactate. Finally, evidence is presented to show that D-lactate and alpha-hydroxybutyrate are mutually exclusive inhibitors of Na+-dependent L-lactate influx. Results from this and recent studies are interpreted as indicating that distinct transport systems serve for unsubstituted and alpha-hydroxymonocarboxylic acids in renal brush-border membrane vesicles.