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.
Spencer
P D
PD
Division of Genetics, Endocrinology and Metabolism, Children's Medical Center, Medical College of Virginia, Richmond.
Medow
M S
MS
Moses
L C
LC
Roth
K S
KS
D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D050260:Carbohydrate Metabolism; D005198:Fanconi Syndrome / Q000378:metabolism; D006537:Heptanoates / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D014443:Tyrosine / Q000097:blood
D000596:Amino Acids; D006537:Heptanoates; D006538:Heptanoic Acids; D014443:Tyrosine; C020804:succinylacetone; D012964:Sodium