Abstract
Hereditary tyrosinemia is an autosomal recessive disease resulting in hepatorenal dysfunction. The renal manifestations of the disease include renal tubular acidosis of the proximal variety, aminoaciduria, glycosuria and phosphaturia comprising the entity known as the Fanconi syndrome. Individuals with this disease excrete large amounts of succinylacetone, a catabolic end-product of tyrosine, in their urine. We have examined in vitro the renal tubular transport interactions of SA with the D-glucose transport analogue, AMG in rat renal tubules.
AMG uptake by the rat renal tubule was markedly inhibited by 4 mM SA in vitro. The effect was immediate in onset, was primarily on substrate entry and was reflected by a 50% decrease in oxygen consumption. On the other hand, 4 mM SA caused no fine structural alterations in mitochondria or brush border membrane. The inhibition of AMG uptake could be reversed by removing SA from the medium, and was non-competitive in nature. These data are consistent with the hypothesis that SA or succinylacetoacetate from which it is derived may be causally related to the Fanconi syndrome in hereditary tyrosinemia. It is concluded that the use of SA for in vitro study of renal tubular transport dysfunction may provide a physiologic model for investigation of the human Fanconi syndrome.
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Tubule, R., Roth, K., Spencer, P. et al. 1251 Effects of Succinylacetone (SA) on Alpha-Methyl-D-1251 Glucoside (AMG) Uptake. Pediatr Res 19, 319 (1985). https://doi.org/10.1203/00006450-198504000-01281
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DOI: https://doi.org/10.1203/00006450-198504000-01281