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J. Biol. Chem., Vol. 262, Issue 27, 13102-13106, 09, 1987

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

B Barbarat and RA Podevin
Department of Physiology, Faculte de Medecine Xavier Bichat, Institut National de la Sante et de la Recherche Medicale, Paris, France.

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.
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