Effects of succinylacetone on the uptake of sugars and amino acids by brush border vesicles.

Infants with hereditary tyrosinemia excrete succinylacetone (SA) in their urine, and suffer from a reversible renal Fanconi syndrome with glycosuria and hyperaminoaciduria. Thus, we have examined the effects of 4 mM SA on rat renal brush border membrane vesicle uptake of sugars and amino acids. SA, unlike sodium maleate, significantly inhibits Na+-dependent vesicular sugar and amino acid uptake. 22Na-uptake, as well as membrane fluidity of the vesicles, are also affected by SA. Inhibition of glycine uptake by SA is reversible and competitive in nature, while alpha-CH3-D-glucoside uptake is non-competitively affected. We conclude, therefore, that SA has a more complex action on the rat renal tubule than sodium maleate, and is likely a much more physiologic model for study of the human renal Fanconi syndrome.