delta-Aminolevulinic acid dehydratase: effects of succinylacetone in rat liver and kidney in an in vivo model of the renal Fanconi syndrome.
Succinylacetone (SA) is a known inhibitor of the heme biosynthetic pathway in liver. We have demonstrated previously the SA enhancement of delta-aminolevulinic acid dehydratase (ALAD) in renal tubules, while this enzyme is known to be impaired by SA in the liver. The present studies, based on in vivo treatment of animals with SA, show equivalent degree of inhibition of specific ALAD activity in liver and kidney. Both tissues evidenced an ability to restore enzyme activity with time, the recovery occurring much more slowly in kidney than in liver. The discrepant in vitro and in vivo effect of SA on renal ALAD may be due to differences between a direct inhibitor-enzyme interaction and inhibitor actions in the living cell, respectively. Persistent tissue levels of SA, consistent with demonstrated SA in plasma and urine, might account for continuing inhibition, with the greatest tissue accumulation in kidney where the substance must be cleared for excretion.
Wyss
P A
PA
Department of Internal Medicine, Medical College of Virginia, Richmond 23298.
Carter
B E
BE
Roth
K S
KS
D000818:Animals; D005198:Fanconi Syndrome / Q000201:enzymology*; D006537:Heptanoates / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009928:Organ Specificity; D000623:Porphobilinogen Synthase / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains
D006537:Heptanoates; C020804:succinylacetone; D000623:Porphobilinogen Synthase