In vivo regulation of delta-aminolevulinate dehydratase activity

• Published in: Toxicology and applied pharmacology Vol. 77; no. 1; p. 66
• Main Authors: Fujita, H, Yamamoto, R, Sato, K, Ikeda, M
• Format: Journal Article
• Language: English
• Published: United States 01.01.1985
• Subjects: Aminolevulinic Acid - pharmacology; Animals; Bone Marrow - analysis; Bone Marrow - metabolism; Enzyme Inhibitors - pharmacology; Glutathione - blood; Glutathione - pharmacology; Lead - blood; Lead - pharmacology; Liver - analysis; Liver - metabolism; Male; Porphobilinogen Synthase - antagonists & inhibitors; Radioimmunoassay; Rats; Rats, Inbred Strains; Zinc - blood; Zinc - pharmacology
• ISSN: 0041-008X
• DOI: 10.1016/0041-008X(85)90268-6

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.