Interaction of zinc and lead on δ-aminolevulinate dehydratase

Finelli, Vincent N.; Klauder, David S.; Karaffa, M.A.; Petering, Harold G.

doi:10.1016/s0006-291x(75)80093-3

Cited by 127 publications

(40 citation statements)

References 18 publications

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“…Rather, they hypothesized that zinc and lead competed for similar binding sites on a metallothionein-like protein in the intestine responsible for metal transport. Interactions between zinc and lead are possible beyond the level of the gastrointestinal tract, however, since zinc added in vitro or given in ii'o has been shown to activate the enzyme 8-aminolevulinic acid dehydratase and to prevent the inhibition of this enzyme by lead (51,52). In fact, concern was expressed that in workers exposed to both zinc and lead the zinc might activate the enzyme enough to mask the excessive lead burden of the body (53).…”

Section: Zinc and Coppermentioning

confidence: 99%

Lead toxicity and nutritional deficiencies.

Levander¹

1979

Environ Health Perspect

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Under appropriate conditions, deficiencies of certain minerals and vitamins as well as high intakes of dietary fat increase the toxicity of a given dose of lead in experimental animals. The severity of lead poisoning can also be increased by the consumption of either deficient or excessive levels of protein. Mineral deficiencies appear to have some of the most profound effects on lead toxicity, since the consequences of plumbism can be exaggerated by feeding diets low in calcium, phosphorus, iron, zinc, and in some cases, copper. Evidence for an antagonism between lead and nutritional levels of selenium is inconclusive. Vitamin E deficiency and lead poisoning interact to produce an anemia in rats that is more severe than that caused by either treatment alone. Lead apparently exerts a pro-oxidant stress on the red cell, thereby causing its accelerated destruction. One of the biochemical mechanisms of lead poisoning may be the disruption of normal membrane architecture, thereby leading to peroxidative damage. Epidemiological surveys have suggested a negative correlation between the poor nutritional status of children with regard to calcium and the concentration of lead in blood. Other examples of potential interactions of mineral status and lead poisoning in humans include the hypothesized hazards of soft water to public health in areas with lead plumbing and the possible role of mineral deficiencies in the etiology of pica. Experimental studies have shown that in some situations combined nutritional deficiencies can have an additive effect in potentiating lead toxicity.

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Section: Zinc and Coppermentioning

confidence: 99%

Lead toxicity and nutritional deficiencies.

Levander¹

1979

Environ Health Perspect

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“…The mechanism by which manganese and zinc inhibit the induction of heme oxygenase is not yet defined, but the blocking action itself is striking and consistent with other data which demonstrate that certain metals can significantly modify the effects produced in biological systems by other metals (9)(10)(11). The findings of this study emphasize the importance of considering the significance of combined rather than single metal exposures in defining the toxicology of these environmental chemicals and they also provide further evidence for the existence of important metal-metal interactions in the regulation of heme metabolism (12,13 25 ,umol/100 g of body weight. Allylisopropylacetamide was administered subcutaneously at a dose of 40 mg/100 g. Control rats received subeutaneous injections of an equivalent volume of normal saline.…”

mentioning

confidence: 59%

“…The effect of manganese on renal heme oxygenase induction was also of great interest with respect to the ability of this metal to apparently remain active in situ for' at least 8 (12,13).…”

mentioning

confidence: 99%

Manganese and zinc blockade of enzyme induction: Studies with microsomal heme oxygenase

Drummond¹,

Kappas²

1979

Proc. Natl. Acad. Sci. U.S.A.

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Heme oxygenase (decyclizing) [heme,hydrogen-donor:oxygen oxidoreductase (a-methene-oxidizing, hydroxylating), EC 1.14.99.3] is greatly induced in the kidney by the administration of nickel or tin. Manganese, when administered simultaneously with nickel or tin in an equimolar amount, substantially inhibited the induction of heme oxygenase. The extent of inhibition was 80% and 98%, respectively. In rats pretreated up to 8 hr with manganese, the level of induction of heme oxygenase by nickel or tin was markedly reduced in a time-dependent fashion. Manganese treatment after the inducing metat was relatively ineffective in preventing the induction of heme oxygenase. Manganese in vitro did not inhibit heme oxygenase in the microsomes isolated from either control or tin-induced rats and in vivo did not increase the rate of catabolism of the induced enzyme. Magnesium was unable to block nickel or tin induction of heme oxygenase. Zinc in equimolar amounts could also substantially reduce the extent o induction of renal heme oxygenase when administered simultaneously with nickel or tin. In addition, simultaneous zinc administration blocked to a considerable extent the induction of hepatic heme oxygenase by nickel, cobalt, or cadmium. These findings indicate the existence of metal-metal interactions that can greatly influence the regulatory mechanism for the induced synthesis of heme oxygenase, the rate-limiting enzyme in heme degradation. Earlier studies from this laboratory showed that a number of transition elements and heavy metals are potent inducers of heme oxygenase (decyclizing) [heme,hydrogen-donor:oxygen oxidoreductase (a-methene-oxidizing, hydroxylating), EC 1.14.99.3] (1-3), the microsomal enzyme that catalyzes the rate-limiting step in the catabolism of heme to bile pigment (4, 5). Concomitant with the metal-induced increase in heme oxygenase there is generally a decrease in microsomal heme and cytochrome P-450 levels and an impairment in the activity of the mixed function oxidase system (2, 3, 6, 7). If these detrimental effects of exogenous metals on heme metabolism could be readily blocked, cellular mechanisms for carrying out cytochrome P-450-dependent detoxification of drugs and related chemicals would be expected to be maintained at normal levels.We report in this communication that the induction of microsomal heme oxygenase by certain trace elements can be prevented by the administration of other metals. Specifically, manganese and zinc are shown to be potent inhibitors of tinand nickel-mediated induction of heme oxygenase in the kidney, whereas zinc can substantially reduce the extent of induction of hepatic heme oxygenase by cobalt, cadmium, and nickel. This inhibition of metal induction of heme oxygenase is associated with a diminution of the decline usually observed in microsomal heme and cytochrome P-450 content as well as in the activity of the mixed function oxidase system. The se-The publication costs of this article were defrayed in part by page charge payment. This article must therefor...

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“…Interactions of lead with zinc have also been discussed by Finelli et al (170) who pointed out that ALA-D is a zinc-dependent enzyme (171) and is completely inhibited by lead.…”

Section: Environmental Health Perspectivesmentioning

confidence: 94%

Factors influencing metabolism and toxicity of metals: a consensus report

1978

Environ Health Perspect

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Interaction of zinc and lead on δ-aminolevulinate dehydratase

Cited by 127 publications

References 18 publications

Lead toxicity and nutritional deficiencies.

Lead toxicity and nutritional deficiencies.

Manganese and zinc blockade of enzyme induction: Studies with microsomal heme oxygenase

Factors influencing metabolism and toxicity of metals: a consensus report

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