Anemia, one consequence of
aluminum toxicity, may be due to inhibition of
enzymes in the
heme biosynthetic pathway. In this study, the in vitro effect of
aluminum on rat liver and erythrocyte
delta-aminolevulinic acid dehydratase (delta-ALA
dehydratase), an
enzyme that is sensitive to a number of
metal ions, was investigated. The presence of 1-10 microM
AlCl3 caused a concentration-dependent inhibition of liver delta-ALA
dehydratase activity. The Ki for AlCl3-induced inhibition of delta-ALA
dehydratase was 4.1 microM, and 10 microM
AlCl3 virtually abolished delta-ALA
dehydratase activity (99% inhibition). Erythrocyte delta-ALA
dehydratase was also inhibited by similar concentrations of
AlCl3 and displayed a Ki of 1.1 microM.
AlCl3 (5 microM) decreased the Vmax by 50% but did not change the Km, suggestive of reversible, noncompetitive inhibition.
Sodium citrate (50 microM) when added with
AlCl3 completely restored delta-ALA
dehydratase activity to basal levels. Thus, disruption of delta-ALA
dehydratase occurred at low micromolar levels of
AlCl3 in vitro, which may help to explain abnormalities in the
heme pathway in cases of
aluminum poisoning.