Nature of inhibition of renal aspartate reabsorption in experimental Fanconi syndrome.

Administration of heavy metals or maleic acid induces a condition resembling the Fanconi syndrome. In the case of metals, an apparently uncompetitive inhibition of reabsorption of amino acids was observed 2 days or longer after injection into rabbits (E. C. Foulkes and S. Blanck, Toxicol. Appl. Pharmacol. 64, 103-107, 1982). Transport of aspartate is now shown to be similarly inhibited by maleic acid and cephaloridin. Because maleic acid, as well as p-chloromercuribenzoate (PCMB) and Cd (in presence of mercaptoethanol), exerts an apparent uncompetitive effect within minutes of injection, the inhibition cannot simply reflect characteristics of regenerating epithelium. At low doses, PCMB inhibits aspartate reabsorption without altering transport of certain neutral amino acids, calcium, or p-aminohippurate. The apparent uncompetitive inhibition of aspartate reabsorption therefore does not connote general cytotoxicity. Metals cause relatively specific effects, manifested by functional lesions at the brush border. The mechanism of the aminoaciduric action of maleic acid remains unclear but cannot, under present conditions, involve back leakage of amino acids into tubular urine.