Renal metabolic/excretory coupling.
Renal metabolic/excretory coupling is the enhancement of urinary excretion dependent upon renal metabolism. The nitrofurothiazoles, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) and 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT), are model compounds used to study metabolic/excretory coupling. FANFT is deformylated to ANFT by renal deformylase enhancing ANFT excretion. In the rat, ANFT excretion after oral FANFT administration was 100-fold greater than ANFT excretion when ANFT was administered. FANFT and ANFT uptake into purified proximal tubules achieved equilibrium within 60 s and was demonstrated in nonviable tubules. FANFT partitioned into oil better than ANFT. Albumin inhibited FANFT and ANFT uptake into oil and decreased tubular uptake by 65%. Tubular FANFT uptake was threefold or greater than that of ANFT uptake with or without albumin. Renal deformylase was predominantly cytosolic and yielded apparent Km and Vmax of 6.7 microM and 6.1 nmol ANFT.min-1.mg protein-1, respectively. Deformylase activity was abolished by boiling, was specific for N-formylated compound, and was not altered by dinitrophenol treatment. Renal metabolic/excretory coupling for FANFT/ANFT combines energy-independent uptake with metabolism (deformylation), resulting in enhanced urinary ANFT excretion.
Spry
L A
LA
Veterans Administration Medical Center, GRECC, St. Louis, MO 63125.
Rubinstein
J
J
Rettke
C
C
Zenser
T V
TV
Davis
B B
BB
D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005200:FANFT / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008657:Metabolic Clearance Rate; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D010130:p-Aminohippuric Acid / Q000378:metabolism
C024885:ANFT; D005200:FANFT; D010130:p-Aminohippuric Acid