delta-Aminolevulinic acid dehydratase in rat liver: studies on the effects of ethanol, acetaldehyde, and B6 vitamers.
Because ethanol ingestion lowers delta-aminolevulinic acid dehydratase (ALAD) activity in liver and red cells, effects of ethanol and acetaldehyde on ALAD in rat liver cytosol were studied. When added to the assay mix, as little as 0.5 mmol/L acetaldehyde competitively inhibited ALAD even in the presence of dithiothreitol, a sulfhydryl reagent. ALAD activity also fell when undiluted cytosol was incubated at 37 degrees with as little as 0.25 mmol/L acetaldehyde for 8 hours before enzyme assay. Inactivation of ALAD by acetaldehyde was prevented by the metabolic inhibitor NaF but not by the aldehyde dehydrogenase inhibitor cyanamide. Incubation of undiluted cytosol with 20 mmol/L ethanol also decreased ALAD activity, but addition of ethanol to the assay mix had no effect. Ethanol-mediated inactivation of ALAD was reduced by inhibition of alcohol dehydrogenase with 4-methylpyrazole, but ALAD activity was not decreased by incubation of undiluted cytosol with acetate or sorbitol or by addition of acetate to the assay mix. The aldehydic B6 vitamers, pyridoxal and pyridoxal phosphate, also inhibited ALAD activity when added to the assay mix. However, these vitamers increased ALAD activity and decreased acetaldehyde-mediated inactivation of ALAD when incubated for 8 hours with undiluted cytosol. We conclude that (1) acetaldehyde decreases ALAD activity both by competitive inhibition with substrate and by inactivation of enzyme protein and that (2) inactivation of ALAD by acetaldehyde may require nonoxidative metabolism of acetaldehyde. The net pharmacologic effect of B6 vitamers on ALAD activity and on inactivation of ALAD by acetaldehyde remains to be determined.
Department of Medicine, Veterans Administration Medical Center, West Haven, Connecticut.
L R
LR
Solomon
J Y
JY
Crouch
D000079:Acetaldehyde / Q000494:pharmacology; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D000431:Ethanol / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D000623:Porphobilinogen Synthase / Q000378:metabolism*; D011736:Pyridoxine / Q000494:pharmacology; D051381:Rats
D000431:Ethanol; D000623:Porphobilinogen Synthase; D000079:Acetaldehyde; D011736:Pyridoxine