Lead, Zinc, and Erythrocyte δ-Aminolevulinic Acid Dehydratase: Relationships in Lead Toxicity

Abstract

A lead-intoxicated patient with extremely high blood lead levels and unexpectedly mild symptoms was studied prior to and following treatment with calcium disodium edetate (ethylenediaminetetraacetic acid) and then prior to and following oral administration of zinc sulfate. During chelation therapy, erythrocyte (delta)-aminolevulinic acid dehydratase (ALAD) activity decreased as blood lead levels fell. Urinary excretion of zinc increased and was more than 3.5 times greater than that of lead. The ratio of blood lead to serum zinc was greatest (1.47) when ALAD activity was lowest. Oral administration of zinc sulfate following chelation therapy resulted in a significant increase in mean ALAD activity. In vitro additions of zinc chloride to the patient's erythrocytes resulted in reactivation of ALAD activity. These studies suggest that zinc is an important element in the ALAD system in man. Zinc may play a protective role in lead toxicity, and zinc supplementation may be a useful adjunct to chelation therapy for lead toxicity.

The in vivo effects of zinc on erythrocyte delta-aminolaevulinic acid dehydratase in man

“…The present findings, however, are consistent with the animal studies of Haeger-Aronsen et al ( 1976) who noted a positive correlation between erythrocyte ALA dehydratase activity and zinc in the plasma of rabbits but were unable to demonstrate any correlation between the enzyme activity and erythrocyte zinc concentrations The present study does not, however, provide any further evidence as to whether the apparent protective role of zinc in lead toxicity (Thomasino et al , 1977) is mediated by the action of zinc on ALA dehydratase.…”

“…It has been shown that other metals besides lead can alter the activity of ALA dehydratase Silver, copper (Gibson et al , 1955), and cadmium (Lauwerys et al , 1973) depressed the activity of the enzyme, whilst other metals, such as zinc and aluminium (Meredith et al , 1977) have been demonstrated to increase the activity of the enzyme Of these, zinc has been shown to have the most profound effect in activating the enzyme in animal studies in vivo and in vitro (Abdulla and HaegerAronsen, 1971 ;Cheh and Neilands, 1973 ;Haeger-Aronson et al , 1976 ;Finelli et al, 1975) As yet, however, there is no evidence to demonstrate that zinc has any effect on ALA dehydratase at physiological concentrations in man although a case study of a lead-poisoned human subject suggested that zinc may have a protective role on the effects of lead toxicity (Thomasino et al , 1977) The purpose of the present study, therefore, was to fully evaluate the value of erythrocyte ALA dehydratase activity as a measure of environmental and occupational lead exposure, in the presence of varying concentrations of zinc.…”

Low Blood Lead Levels Do Not Appear to Be Further Reduced by Dietary Supplements

“…However, Barltrop and Khoo (1975) found that low Zn, Fe, Mn, Cu, iodine, and molybdenum did not have any effect on Pb absorption in rats. Results have been mixed for the limited human studies that have addressed the relationship between Zn and Pb ( Bárány et al 2005 ; Flanagan et al 1982 ; Lauwerys et al 1983 ; Thomasino et al 1977 ). For example, in a study of 85 fasting males and females, Flanagan et al (1982) observed that Pb retention was not related to body Fe burden or even a 10-fold molar excess of Fe, of Zn, Co, or Ca.…”

Lead Toxicity and Nutritional Deficiencies

“…Thomasino et al (58) have suggested that zinc supplementation may be a useful adjunct to chelation therapy for lead toxicity.…”