delta-Aminolevulinic acid dehydratase: is there a form unique to renal cortex?
Succinylacetone (SA) is known to be a potent inhibitor of delta-aminolevulinic acid dehydratase (ALAD) in the liver. We have examined the effects of SA on the rat renal cortical enzyme, our observations indicating very different behaviour of renal versus hepatic ALAD with SA treatment. While the temperature response of ALAD in both tissues was similar, addition of 4 mmol/l SA inhibited liver ALAD at 37 and 55 degrees C and enhanced renal ALAD activity 2- to 3-fold at each temperature. This increase in renal ALAD was progressive with SA concentrations form 1 to 10 mmol/l. A pH titration curve for both liver and kidney ALAD showed the hepatic enzyme to have a single pH optimum, while the renal enzyme had two, each of which was distinct from that in liver. Kinetic studies with and without 4 mmol/l SA over a 50-fold ALA concentration range indicated SA-induced enhancement of renal ALAD over the entire range at both pH optima. Using 14C-labelled ALA, we have confirmed these observations made on the basis of a colorimetric assay for PBG, the enzyme product. We conclude that renal ALAD may be a different molecular species from the liver enzyme. Further studies may clarify the significance of these observations to renal heme synthesis.
Roth
K S
KS
Department of Pediatrics, Medical College of Virginia, Richmond.
Spencer
P D
PD
Moses
L C
LC
Carter
B E
BE
D000818:Animals; D006537:Heptanoates / Q000494:pharmacology*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007527:Isoenzymes / Q000378:metabolism*; D007672:Kidney Cortex / Q000201:enzymology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D009928:Organ Specificity; D000623:Porphobilinogen Synthase / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013816:Thermodynamics
D006537:Heptanoates; D006538:Heptanoic Acids; D007527:Isoenzymes; C020804:succinylacetone; D000623:Porphobilinogen Synthase