Metal‐Induced Alterations of δ‐Aminolevulinic Acid Dehydratase

@article{Bernard1987MetalInducedAO,
  title={Metal‐Induced Alterations of $\delta$‐Aminolevulinic Acid Dehydratase},
  author={Alfred Bernard and Robert R. Lauwerys},
  journal={Annals of the New York Academy of Sciences},
  year={1987},
  volume={514}
}
  • A. BernardR. Lauwerys
  • Published 1 December 1987
  • Biology, Chemistry
  • 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… 

Pyruvate Kinase Activity and δ-Aminolevulinic Acid Dehydratase Activity as Biomarkers of Toxicity in Workers Exposed to Lead

Investigating the effect of Pb2+ on the activity of the thiolenzymes δ-ALAD and PK and on the concentration of glutathione, a nonenzymatic antioxidant defense, in erythrocytes from Pb-exposed workers indicated an apparent dose-effect relationship between PK activity and BPb.

Delta-aminolevulinic acid dehydratase (ALAD) characterization and use in metal exposure assessments

Five avian and two small mammal species were collected from the Anaconda Smelter Superfund site and assessed for ALAD activity as a biomarker of exposure to smelter-related metal contamination.

Dichotomous effects of lead acetate on the expression of metallothionein in the liver and kidney of mice.

The data suggest that Pb exerts a dual effect on MT expression; enhancement of MT gene transcription both in the liver and kidney and suppression of MT mRNA translation in the kidney.

Comparative inhibition of enzymes of human erythrocytes and plasma in vitro by agricultural chemicals

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.

Sensitivity of delta-ALA-D (E.C. 4.2.1.24) of rats to metals in vitro depends on the stage of postnatal growth and tissue.

References

SHOWING 1-10 OF 66 REFERENCES

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) 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.

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.

Mechanism of renal lead-binding protein reversal of delta-aminolevulinic acid dehydratase inhibition by lead.

  • P. GoeringB. Fowler
  • Biology, Chemistry
    The Journal of pharmacology and experimental therapeutics
  • 1985
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

5-Aminolaevulinic acid dehydratase: structure, function, and mechanism.

  • D. Shemin
  • Biology, Chemistry
    Philosophical transactions of the Royal Society of London. Series B, Biological sciences
  • 1976
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

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.
...