title: Renal heme metabolism in hereditary tyrosinemia: use of succinylacetone in rat renal tubules.
abstract: Succinylacetone (SA), a metabolic end-product found in urine from individuals with hereditary tyrosinemia and associated renal Fanconi syndrome and a known inhibitor of hepatic 5-aminolevulinic acid dehydratase (ALAD), has been used to study heme metabolism in isolated rat renal tubules. Heme biosynthetic porphyrin precursors are increased selectively in the presence of 4 mmol/1 SA. Total porphyrin content of the tubules are increased approximately 2-fold, while both ferrochelatase and heme oxygenase activities remain unaffected by SA. Nonetheless, total heme content is reduced, as was incorporation of radioactive label from amino[14C]levulinic acid. Cytochrome P-450 content remained unaffected. Impairment of iron uptake and/or transport within the cell or enhancement of heme catabolism via a non-heme oxygenase-dependent pathway could explain the observations.
authors.affiliation: Department of Medicine, Medical College of Virginia, Richmond 23298.
authors.forename: P A
authors.initials: PA
authors.lastname: Wyss
authors.forename: B E
authors.initials: BE
authors.lastname: Carter
authors.forename: S B
authors.initials: SB
authors.lastname: Boynton
authors.forename: E
authors.initials: E
authors.lastname: Connor
authors.forename: B
authors.initials: B
authors.lastname: Fowler
authors.forename: K S
authors.initials: KS
authors.lastname: Roth
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005294:Ferrochelatase / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006537:Heptanoates / Q000494:pharmacology*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011166:Porphyrins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D006537:Heptanoates; D011166:Porphyrins; D014443:Tyrosine; D006418:Heme; C020804:succinylacetone; D003577:Cytochrome P-450 Enzyme System; D006419:Heme Oxygenase (Decyclizing); D005294:Ferrochelatase