Metal‐Induced Alterations of δ‐Aminolevulinic Acid Dehydratase

@article{Bernard1987MetalInducedAO,
  title={Metal‐Induced Alterations of $\delta$‐Aminolevulinic Acid Dehydratase},
  author={A. Bernard and Robert Lauwerys},
  journal={Annals of the New York Academy of Sciences},
  year={1987},
  volume={514}
}
  • A. Bernard, R. Lauwerys
  • Published 1 December 1987
  • Chemistry, Medicine
  • Annals of the New York Academy of Sciences
ALAD is a cytoplasmic enzyme that catalyzes the second step of the heme biosynthesis pathway, that is, the condensation of two molecules of delta-aminolevulinic acid into porphobilinogen. ALAD is a zinc-dependent enzyme; thiol groups are essential for its activity; and in vitro experiments show that ALAD can be activated or inhibited by several metal ions including A;3+, Pb2+, Cd2+, Hg2+, Ag2+, and Cu2+. To explain these effects, it has been postulated that metals bind to thiol groups of… 
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Pyruvate Kinase Activity and d-Aminolevulinic Acid Dehydratase Activity as Biomarkers of Toxicity in Workers Exposed to Lead
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SOD was the enzyme that was most sensitive to all the agricultural-chemicals tested in this study and the inhibition of these enzymes will enable the development of a sensitive biomarker and the assessment of long term health risks in farm workers.
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References

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TLDR
The effects of twelve metals at various concentrations ranging from 10(-41 to 10(-7) M) M have been studied on delta-aminolaevulinic acid dehydratase 9000 fold (ALA-D), isolated and purified from human red cells, and agree with the following hypothesis: according to their structure, metals would bind the enzyme in one or several allosteric sites, and induce an allosterics transposition to the active or inactive form of enzyme.
The effect of metal ions on the activity of delta-aminolevulinic acid dehydratase.
The effects of lead, iron, copper, and zinc ions on delta-aminolevulinic acid dehydratase from red blood cell haemolysates in humans, both in the absence and presence of plasma proteins, have been
Mechanism of porphobilinogen synthase. Requirement of Zn2+ for enzyme activity.
TLDR
It appears that Zn2+ does not participate in substrate binding nor in the maintenance of the quaternary structure of the enzyme, and Cd2+ was the only other element found which restored activity to the apoenzyme.
The role of zinc with special reference to the essential thiol groups in delta-aminolevulinic acid dehydratase of bovine liver.
TLDR
It is apparent that the activity ofelta-Aminolevulinic acid dehydratase depends on the essential SH groups, and the zinc is not absolutely essential for the activity but may be required to prevent the essentialSH groups from autooxidation by coordination.
Mechanism of renal lead-binding protein reversal of delta-aminolevulinic acid dehydratase inhibition by lead.
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  • Chemistry, Medicine
    The Journal of pharmacology and experimental therapeutics
  • 1985
TLDR
Addition of semipurified PbBP to liver delta-aminolevulinic acid dehydratase (ALAD) reaction mixtures reverses inhibition of this enzyme by lead and thus provides an explanation for the relative insensitivity of renal ALAD to lead inhibition in vivo and in vitro.
Antagonistic effects of zinc and aluminum on lead inhibition of delta-aminolevulinic acid dehydratase.
In vitro and in vivo studies regarding the influence of metals on delta-aminolevulinic acid dehydratase activity in erythrocytes indicate that a lead concentration of 4 micrometer/l completely
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  • Medicine, Biology
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  • 1976
TLDR
It appears that only four of the eight subunits ofelta-Aminolaevulinic acid dehydratase form a Schiff base with the substrate indicating that the enzyme exhibits the phenomenon of either half-site reactivity or negative cooperativity.
Increase in the amount of erythrocyte δ-aminolevulinic acid dehydratase in workers with moderate lead exposure
TLDR
An apparent increase in the amount of ALA-D in human erythrocytes might be a result of the function to overcome the inhibition of the enzyme in bone marrow cells during lead exposure, and these findings may throw light on the danger to human health of low-level lead toxicity.
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