Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease

Wayne State University School of Medicine, Department of Oncology, Barbara Ann Karmanos Cancer Institute, Detroit, MI.
Advances in Nutrition (Impact Factor: 4.71). 03/2013; 4(2):176-190. DOI: 10.3945/an.112.003210
Source: PubMed


The essentiality of zinc in humans was established in 1963. During the past 50 y, tremendous advances in both clinical and basic sciences of zinc metabolism in humans have been observed. The major factor contributing to zinc deficiency is high phytate-containing cereal protein intake in the developing world, and nearly 2 billion subjects may be zinc deficient. Conditioned deficiency of zinc has been observed in patients with malabsorption syndrome, liver disease, chronic renal disease, sickle cell disease, and other chronic illnesses. Major clinical problems resulting from zinc deficiency in humans include growth retardation; cell-mediated immune dysfunction, and cognitive impairment. In the Middle East, zinc-deficient dwarfs did not live beyond the age of 25 y, and they died because of intercurrent infections. In 1963, we knew of only 3 enzymes that required zinc for their activities, but now we know of >300 enzymes and >1000 transcription factors that are known to require zinc for their activities. Zinc is a second messenger of immune cells, and intracellular free zinc in these cells participate in signaling events. Zinc has been very successfully used as a therapeutic modality for the management of acute diarrhea in children, Wilson's disease, the common cold and for the prevention of blindness in patients with age-related dry type of macular degeneration and is very effective in decreasing the incidence of infection in the elderly. Zinc not only modulates cell-mediated immunity but is also an antioxidant and anti-inflammatory agent.

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    • "Zn(II) is essential for all living organisms since it is used as cofactor in a very wide number of enzymes and proteins involved in central metabolic pathways, in the protection against oxidative damage, in the control of gene expression, and in immune response [1] [2] [3] [4]. "
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    ABSTRACT: Background: Under conditions of Zn(II) deficiency, the most relevant high affinity Zn(II) transport system synthesized by many Gram-negative bacteria is the ZnuABC transporter. ZnuABC is absent in eukaryotes and plays an important role in bacterial virulence. Consequently, ZnuA, the periplasmic component of the transporter, appeared as a good target candidate to find new compounds able to contrast bacterial growth by interfering with Zn(II) uptake. Methods: Antibacterial activity assays on selected compounds from and in-house library against Salmonella enterica serovar Typhimurium ATCC14028 were performed. The X-ray structure of the complex formed by Se-ZnuA with an active compound was solved at 2.15Å resolution. Results: Two di-aryl-pyrrole-hydroxamic acids differing in the position of a chloride ion, RDS50 ([1-[(4-chlorophenyl)methyl]-4-phenyl-1H-pyrrol-3-hydroxamic acid]) and RDS51 (1-[(2-chlorophenyl)methyl]-4-phenyl-1H-pyrrol-3-hydroxamic acid) were able to inhibit Salmonella growth and its invasion ability of Caco-2 cells. The X-ray structure of Se-ZnuA containing RDS51 revealed its presence at the metal binding site concomitantly with Zn(II) which is coordinated by protein residues and the hydroxamate moiety of the compound. Conclusions: Two molecules interfering with ZnuA-mediated Zn(II) transport in Salmonella have been identified for the first time. The resolution of the Se-ZnuA-RDS51 X-ray structure revealed that RDS51 is tightly bound both to the protein and to Zn(II) thereby inhibiting its release. These features pave the way to the rational design of new Zn(II)-binding drugs against Salmonella. General significance: The data reported show that targeting the bacterial ZnuABC transporter can represent a good strategy to find new antibiotics against Gram-negative bacteria.
    Full-text · Article · Dec 2015 · Biochimica et Biophysica Acta (BBA) - General Subjects
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    • "In addition , it acts in fatty acid metabolism and reduces oxidative stress. Zinc is also essential during development, and severe deficiency results in heavy anemia, mental retardation, and body underdevelopment [1] [2]. More interestingly, zinc also appears to be involved in certain behavioral processes. "
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    ABSTRACT: Zinc is an essential trace element for humans and animals, being located, among other places, in the synaptic vesicles of cortical glutamatergic neurons and hippocampal mossy fibers in the brain. Extracellular zinc has the potential to interact with and modulate many different synaptic targets, including glutamate and GABA receptors. Because of the central role of these neurotransmitters in brain activity, we examined in this study the sleep-promoting activity of zinc by monitoring locomotor activity and electroencephalogram after its administration to mice. Zinc-containing yeast extract (40 and 80 mg/kg) dose dependently increased the total amount of non-rapid eye movement sleep and decreased the locomotor activity. However, this preparation did not change the amount of rapid eye movement sleep or show any adverse effects such as rebound of insomnia during a period of 24 h following the induction of sleep; whereas the extracts containing other divalent cations (manganese, iron, and copper) did not decrease the locomotor activity. This is the first evidence that zinc can induce sleep. Our data open the way to new types of food supplements designed to improve sleep. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jun 2015 · Molecular Nutrition & Food Research
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    • "Zinc evoked a concentrationdependent increase in the viability of the cells at lower range and decrease in the viability at higher range. At lower range of concentration cell were able to grow at higher rates [23] [24] [25]. Apart from this normal cell survived highest concentration of Zinc supplementation i.e. 80 µM, than that of cancer cells. "
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    ABSTRACT: — Zinc is the most abundant trace element which has role in genetic stability and function, present in the cell nucleus, nucleolus and chromosomes, and stabilizes the structure of DNA, RNA and ribosomes and found in many Zinc binding proteins. The purpose of this study is to access the Zinc cytotoxicity, total cellular Zinc content and total Zinquin Acid (Fluorophore) interaction with cellular Zinc in response to six different Zinc gradient medium using MTT assay, Atomic absorption spectroscopy and Fluorescence spectroscopy respectively. Statistical analysis one way ANOVA and Tukey HSD test for mean comparison was performed. Our findings are, significant differences on normal cell line survival of 108.7% at 10 µM supplemented medium was seen. Cytotoxicity was seen at 80 µM of 89.78% and 86.46% in MDA-MB-231 and U-87-MG Cell lines respectively. Significant increase in cellular influx and accumulation of Zn2+ ions was observed in all cell lines. Fluorescence intensity emission peak response increased with supplementation of gradient medium, which supported the hypothesis of increased cellular Zinc accumulation, λ-max shifting to shorter wavelength i.e. idea supports blue shift emission of Zinquin Acid which interacts not only with free labile Zinc ions but with Zinc bound proteins. Zinc based fluorescence probes help detection of altered expression of Zinc.
    Full-text · Article · Jan 2015
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