KINETICS OF ALUMINUM-INDUCED INHIBITION OF DELTA-AMINOLEVULINIC ACID DEHYDRATASE IN-VITRO

Anemia, one consequence of aluminum toxicity, may be due to inhibition of enzymes in the heme biosynthetic pathway. In this study, the in vi tro effect of aluminum on rat liver and erythrocyte delta-aminolevulin ic acid dehydratase (delta-ALA dehydratase), an enzyme that is sensiti ve to a number of metal ions, was investigated. The presence of 1-10 m u M AlCl3 caused a concentration-dependent inhibition of liver delta-A LA dehydratase activity. The K-i for AlCl3-induced inhibition of delta -ALA dehydratase was 4.1 mu M, and 10 mu M AlCl3 virtually abolished d elta-ALA dehydratase activity (99% inhibition). Erythrocyte delta-ALA dehydratase was also inhibited by similar concentrations of AlCl3 and displayed a K-i of 1.1 mu M. AlCl3 (5 mu M) decreased the V-max by 50% but did not change the K-m, suggestive of reversible, noncompetitive inhibition. Sodium citrate (50 mu M) when added with AlCl3 completely restored delta-ALA dehydratase activity to basal levels. Thus, disrupt ion of delta-ALA dehydratase occurred at low micromolar levels of AlCl 3 in vitro, which may help to explain abnormalities in the heme pathwa y in cases of aluminum poisoning.