AJP - Renal Physiology, Vol 254, Issue 1 145-F152, Copyright © 1988 by American Physiological Society
Renal metabolic/excretory coupling
L. A. Spry, J. Rubinstein, C. Rettke, T. V. Zenser and B. B. Davis
Veterans Administration Medical Center, GRECC, St. Louis, MO 63125.
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.
