title: Renal Fanconi syndrome: developmental basis for a new animal model with relevance to human disease.
abstract: Using succinylacetone (SA), a metabolite of tyrosine excreted in excess by infants and children with hereditary tyrosinemia and the renal Fanconi syndrome (FS), we have investigated developmentally-related membrane transport events leading to emergence of the generalized renal tubular dysfunction seen in human FS. SA was found to impair sugar and amino acid uptake by both newborn renal tubules and 7-day renal brush-border membrane vesicles (BBMV). This impairment by SA was due in part to a slowing of substrate cotransport rate of 22Na+-entry into BBMV. Concentration-dependent uptake studies indicated SA inhibited the newborn high-affinity transport systems for sugars and amino acids. SA also caused an increase in membrane fluidity and a shift in the thermotropic transition temperature. The demonstrated dual nature of SA's effect on membrane fluidity and O2 consumption, together with the relative contribution of each component to SA-induced transport impairment helps to provide a basis for an understanding of the age-related increases in glucosuria, aminoaciduria and natriuria seen in infants with FS.
authors.affiliation: Department of Pediatrics, Medical College of Virginia, Richmond 23298.
authors.forename: K S
authors.initials: KS
authors.lastname: Roth
authors.forename: M S
authors.initials: MS
authors.lastname: Medow
authors.forename: L C
authors.initials: LC
authors.lastname: Moses
authors.forename: P D
authors.initials: PD
authors.lastname: Spencer
authors.forename: S M
authors.initials: SM
authors.lastname: Schwarz
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport / Q000187:drug effects; D050260:Carbohydrate Metabolism; D004195:Disease Models, Animal; D005198:Fanconi Syndrome / Q000378:metabolism*; D005454:Fluorescence Polarization; D006537:Heptanoates / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D007700:Kinetics; D008560:Membrane Fluidity / Q000187:drug effects; D008871:Microvilli / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000378:metabolism
chemical_list: D000596:Amino Acids; D006537:Heptanoates; D006538:Heptanoic Acids; D012965:Sodium Chloride; C020804:succinylacetone