Succinylacetone effects on renal tubular phosphate metabolism: a model for experimental renal Fanconi syndrome.

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  • Author(s): Roth KS;Roth KS; Carter BE; Higgins ES
  • Source:
    Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) [Proc Soc Exp Biol Med] 1991 Apr; Vol. 196 (4), pp. 428-31.
  • Publication Type:
    Journal Article; Research Support, U.S. Gov't, P.H.S.
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Blackwell Science [etc.] Country of Publication: United States NLM ID: 7505892 Publication Model: Print Cited Medium: Print ISSN: 0037-9727 (Print) Linking ISSN: 00379727 NLM ISO Abbreviation: Proc Soc Exp Biol Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: Malden, MA [etc.] Blackwell Science [etc.]
    • Subject Terms:
      Disease Models, Animal*; Fanconi Syndrome/*metabolism ; Heptanoates/*pharmacology ; Kidney Tubules/*drug effects ; Phosphates/*metabolism; Adenosine Triphosphate/metabolism ; Animals ; Cells, Cultured ; Glutamates/metabolism ; Glutamic Acid ; In Vitro Techniques ; Kidney Tubules/metabolism ; Malates/metabolism ; Male ; Microvilli/metabolism ; Mitochondria/metabolism ; Pyruvates/metabolism ; Pyruvic Acid ; Rats ; Rats, Inbred Strains ; Succinates/metabolism ; Succinic Acid ; Time Factors
    • 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.
    • Grant Information:
      R01 AM35319 United States AM NIADDK NIH HHS
    • Accession Number:
      0 (Glutamates)
      0 (Heptanoates)
      0 (Malates)
      0 (Phosphates)
      0 (Pyruvates)
      0 (Succinates)
      3KX376GY7L (Glutamic Acid)
      51568-18-4 (succinylacetone)
      817L1N4CKP (malic acid)
      8558G7RUTR (Pyruvic Acid)
      8L70Q75FXE (Adenosine Triphosphate)
      AB6MNQ6J6L (Succinic Acid)
    • Publication Date:
      Date Created: 19910401 Date Completed: 19910426 Latest Revision: 20200930
    • Publication Date:
      20231215
    • Accession Number:
      10.3181/00379727-196-43211
    • Accession Number:
      1672565