Abstract

Metals play a very significant role in cellular metabolism. Many essential heavy metals are cofactors: copper (Cu), zinc (Zn), Iron (Fe), and cobalt (Co) play vital roles in respiration, electron transport chain, cell division, and diverse types of enzymatic reactions, bimolecular synthesis and immunological responses of the body. Fe is specifically found in hemoglobin, myoglobin, cytochromes (a, b, c), catalase, aconitase, succinate dehydrogenase, aldehyde oxidase, peroxidases, tryptophan 2,3-dioxygenase and many more enzymes (Cassat and Skaar 2013). Cu is required for tyrosinase, superoxide dismutase, cytochrome c oxidase, ceruloplasmin, and dopamine-β-hydoxylase (Desai and Kaler 2008). Similarly, proper protein folding, conformational and configurational alterations and activity, DNA replication, male fertility and growth hormone synthesis and activity are mediated by Zn (Foresta et al. 2014). Co is required for vitamin B12 synthesis (Lindsay and Kerr 2011). Specific protein transporters are responsible for metals homeostasis in the body as they actively take part in the uptake, distribution, storage, and excretion of metal ions inside the body. Similarly, the vacuolar systems of eukaryotic cells store metal ions and transport to various sites of the cell, particularly to the cell membranes via the secretory pathway. Metal ions are also abundantly found in cell organelles such as peroxisome, chloroplasts, and mitochondria. Transporter proteins such as Ctr1, Ctr2, Atox1, CCS, Cox1, Ceruloplasmin, ATP7A, ATP7B, and metallothioneins are responsible for regulation of cellular copper content. Disturbance in the metal homeostasis may result in severe clinical contraindications and critical metabolic disorder leading to morbidity and mortality. Mutation in ATP7A and ATP7B gene are reported to cause Menkes and Wilson diseases (WD) respectively. Deficiency in Cu is observed in Menkes disease, whereas WD is characterized by the accumulation of Cu in the liver, brain and other organs (Kozlowski et al. 2009, Gaetke et al. 2014) 21Transferrin, ceruloplasmin, hephaestin, ferroportin, and divalent metal transporter 1 (DMT1) are responsible for homeostasis of Fe, impairment of which may lead to Fe-deficiency anemia, hemochromatosis, Huntington’s chorea, Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis (Britton et al. 2002, Carocci et al. 2018). Zinc transporter families (ZnT and ZIP) together with metallothioneins help in Zn homeostasis as the ZnT family decreases intracellular zinc level, while the ZIP family plays a vital role in increasing intracellular Zn levels by importing zinc ions from the extracellular space into the cytoplasm (Fukada et al. 2011). Heavy metal concentrations are rapidly increasing in water and soils at an alarming rate during the last few decades owing to the increased levels of electronic waste, fossil fuel burning, disposal of municipal wastes, mining and smelting, and application of fertilizer, pesticides, and sewage. Heavy metals are lethal because of their non-biodegradable nature and high cytotoxicity. Even low concentrations of nonessential heavy metals (As, Hg, Pb, and Cd) can lead to severe health risks, while essential metals such as Zn, Cu, and Fe may become toxic if they exceed their threshold levels (Hu and Cheng 2013, Li et al. 2014, Wu et al. 2015a, Kapusta and Sobczyk 2015). Heavy metal pollution poses a global threat due to its deleterious effects on metabolic processes in biological systems. Industrial effluents are considered the key source of hazardous metals that can cause severe toxicity depending on solubility, concentration, pH and other associated suspended solids. The closing and flooding of mines may also generate large volumes of water contaminated with metals (U, Sn, Cu, As, Fe) (Diels et al. 2003). Conformational alteration of nucleic acids and proteins due to these metals can cause long term patho-physiological defects. Heavy metals that are a prime cause of environmental concern include chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), molybdenum (Mo), silver (Ag), mercury (Hg), cadmium (Cd) and nickel (Ni). Other metallic elements such as aluminum (Al), tin (Sn), lead (Pb) and bismuth (Bi) and metalloids such as arsenic (As), antimony (Sb) and selenium (Se) are also considerably toxic. Cu is abundant in acid mine drainage (Kim et al. 2019). For these reasons, when these metals are discharged in the effluents of metal plating, tannery, paint, dyeing, and smelting industries and enter a wastewater treatment plant, they should be effectively removed during the treatment processes.

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