title: Succinylacetone effects on renal tubular phosphate metabolism: a model for experimental renal Fanconi syndrome.
abstract: Phosphaturia is a prominent component of the renal Fanconi syndrome associated with the autosomal recessive disease, hereditary tyrosinemia. Succinylacetone (SA), the metabolic by-product of the enzyme deficiency, can be shown to produce multiple adverse effects on rat renal epithelial cell function in vitro. With the use of this compound, we have examined its interaction with Pi handling by the renal tubule cell in order to form a basis for understanding the effects of endogenously generated SA in causing phosphaturia in the genetically affected kidney. In this report we have shown complete inhibition of sodium-dependent phosphate uptake by renal brush border membrane vesicles, decreased ATP production by the SA-exposed renal tubule, and reversible inhibition of State 3 oxidation of glutamate by isolated renal mitochondria. We conclude that the phosphaturia observed in hereditary tyrosinemia results from multiple metabolic effects of SA on the renal tubule which are additive and lead to intracellular Pi depletion and diminished ATP production.
authors.affiliation: Department of Pediatrics, Medical College of Virginia, Richmond 23298.
authors.forename: K S
authors.initials: KS
authors.lastname: Roth
authors.forename: B E
authors.initials: BE
authors.lastname: Carter
authors.forename: E S
authors.initials: ES
authors.lastname: Higgins
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005198:Fanconi Syndrome / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006537:Heptanoates / Q000494:pharmacology*; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D008293:Malates / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid; D013997:Time Factors
chemical_list: D005971:Glutamates; D006537:Heptanoates; D008293:Malates; D010710:Phosphates; D011773:Pyruvates; D013386:Succinates; D018698:Glutamic Acid; C020804:succinylacetone; C030298:malic acid; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D019802:Succinic Acid