Developmental Aspects of Maleic Acid-induced Inhibition of Sugar and Amino Acid Transport in the Rat Renal Tubule

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Abstract
Summary: The transport of α-aminoisobutyric acid and α-methyl-D-glucoside by isolated renal tubules from Sprague-Dawley rats at different stages of development follows a separate age-dependent pattern for each substrate. The effects of 6 mM maleic acid on transport processes differ for amino acids and sugars and become manifest at distinct points during development. Maximum inhibition by maleic acid occurs at a time subsequent to maturity of these transport systems. In an effort to explain these transport phenomena, the uptake and metabolism of 14C-labeled maleic acid by the newborn or adult renal tubule was studied, showing significant binding by the tubule membrane, penetration of the cell by diffusion, and no conversion to 14CO2. Maleic acid has no demonstrable effect on the membrane-associated enzymes which are thought to play a role in the transport of small molecules. Speculation: Although the mechanism by which maleic acid inhibits the transport of sugars and amino acids hi the adult rat tubule preparation remains unexplained, it is clear that its effects are age-related and independent of the maturation of these transport systems. This observation is consistent with the delayed appearance of the Fanconi syndrome seen in human cystinosis, and suggests that the progressive tubular dysfunction in this syndrome and in the maleic acid model is secondary to genetically directed intracellular metabolic changes expressed during development.