Postulated mode of action of metals on purified human ALA-dehydratase (EC 4-2-1-24).
The effects of twelve metals at various concentrations ranging from 10(-41 to 10(-7) M have been studied on delta-aminolaevulinic acid dehydratase 9000 fold (ALA-D), isolated and purified from human red cells. The results obtained are in very good agreement with those of many authors: zinc, a constitutive element of the enzyme, behaves as an activator at low concentration, and an inhibitor at higher concentrations. The same effect is noted with aluminium, cadmium, mercury and tin. The manganese has a poor inhibitory action, copper and lead are powerful inhibitors of the enzyme. The other metals studies have no noticiable effect on ALA-D. These results agree with the following hypothesis: according to their structure, metals would bind the enzyme in one or several allosteric sites, and induce an allosteric transposition to the active or inactive form of enzyme.
D000535:Aluminum / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008670:Metals / Q000494:pharmacology*; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015032:Zinc / Q000494:pharmacology
D008670:Metals; D000535:Aluminum; D000623:Porphobilinogen Synthase; D015032:Zinc