In vivo regulation of delta-aminolevulinate dehydratase activity.
The interrelationships among purified delta-aminolevulinate dehydratase (ALA-D; EC 4.2.1.24) activity, Pb, and ALA-D concentrations were studied in vitro. The ratio of Pb to the ALA-D subunit, but not the Pb concentration, determined the relative activity of ALA-D, indicating the significance of the amount of ALA-D in studying the mechanism of enzyme inhibition by Pb. To elucidate the in vivo mechanisms of ALA-D regulation, male Wistar rats, 6 months old, were treated with Pb, Zn, and glutathione (GSH) separately or in combination for 130 days. After Pb administration, the amount of ALA-D, as determined by radioimmunoassay, increased in the presence and in the absence of the Zn-GSH pretreatment, even if the enzyme activity were higher (the Zn-GSH-Pb-treated rats) than that of the control. Zn and GSH restored the enzyme activity in vivo synergistically. Since immunochemical study showed the identity of the liver ALA-D with the erythroid ALA-D, the liver and erythroid data were pooled to quantify the interrelationship among ALA-D activity, and Pb, Zn, SH, and the enzyme concentrations. The equation was the relative activity of ALA-D (%) = 0.256.[Pb/ALA-D subunit]2 - 9.56.[Pb/ALA-D subunit] - 0.000281.[square root Zn.SH/ALA-D subunit]2 + 0.0898..[square root Zn.SH/ALA-D subunit] + 33.6 (multiple correlation coefficient = 0.909, n = 108, p less than 0.01). The result indicated that 83% of the in vivo regulation of ALA-D activity is explained when the four factors, Pb, Zn, SH, and ALA-D concentrations, are considered in combination.
D000622:Aminolevulinic Acid / Q000494:pharmacology; D000818:Animals; D001853:Bone Marrow / Q000032:analysis / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000097:blood / Q000494:pharmacology*; D007854:Lead / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000032:analysis / Q000378:metabolism; D008297:Male; D000623:Porphobilinogen Synthase / Q000037:antagonists & inhibitors*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc / Q000097:blood / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007854:Lead; D000622:Aminolevulinic Acid; D000623:Porphobilinogen Synthase; D005978:Glutathione; D015032:Zinc