Manual Metallomics and the Cell

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Met Ions Life Sci. ; doi: /_1. Metallomics and the cell: some definitions and general comments. Banci L(1), Bertini I.
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Cells acquire many mechanisms so as to sustain copper homeostasis such as; the protein-mediated intracellular delivery of copper to target proteins. This is consummated by a group of proteins, the copper chaperons, which conserved proteins present in prokaryotes and eukaryotes. The copper ion incorporation into SOD1 requires a Cu metallochaperone [67]. Metallochaperones incorporating metals other than copper involve similar cofactor trafficking pathways. However, the chaperones integrating metals besides copper are not present in eukaryotes.

The ArsD, arsenic chaperone present in Escherichia coli has been established to transfer trivalent arsenic to ArsA. The affinity for arsenite increases as ArsA and ArsD interact. This enhances arsenite extrusion even at lower arsenite concentrations as the activity of ATPase increases. Thus, to prevent intracellular toxicity of arsenite, cells exploit arsenic chaperones [70]. Additionally, proteins which bind nickel is described which may promote metal insertion to the enzymes requiring nickel such as urease, Co-dehydrogenase, Ni-superoxide dismutase, glyoxidenalase etc.

Prokaryotes do not need metal carriers such as COX17 as intracellular compartmentalization is not present is prokaryotes as in eukaryotes. However, in the periplasm of prokaryotes and in gram-negative bacteria cupro-proteins are present.

Metallomics 12222

In the gram-negative bacteria, the porins are located in the peripheral membrane through which metals diffuse from the external medium [71]. The proteins like soluble periplasm protein CucA acquire the appropriate metals and export them in unfurled form through the secretory pathway. The isolated CopZ has potential to contribute copper to CopY for a transcription factor.

Several biological processes require metal-ion binding proteins. Metallothionein is rich in cysteine, low molecular weight protein family in animals, angiosperms, eukaryotes and few prokaryotes.

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Metallothioneins contain metal ions viz. These clusters bind heptad of metal ions Me through thiolate coordination [75]. Biosynthesis of MTs is induced by several agents and is coordinated at the level of transcription.

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MTs sequester mainly metals which are non-essential [76]. Metabolomics, a rapidly developing technology deals with metabolome which is described as the metabolites compilation of the cell [77]. Metabolic fingerprinting, targeted analysis and metabolite profiling are the major approaches presently adopted in metabolomics related research [78].


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The three components are significant in metabolomics in order to carry out such processes: 1 antioxidants 2 stress by-products due to disruption of homeostasis; and 3 molecule involved in signal transduction responsible for adaptation response. The molecules involved in signal transduction are either recurrently synthesized or compounds liberated from conjugated forms such as salicylic acid [79].

The metals and ligands interaction is a significant area of metallomics research. The defensive mechanisms of numerous organisms against toxic metals comprise of many organic acids such as succinate, malate, oxalate etc. Hyper accumulating plants developing metal homeostasis are of particular interest. They can live and reproduce in metal-rich environments [82]. In such plant cells, the complexity of metals leads to many relatively poorly characterized metal complexes. The study of detoxification controlling mechanisms can benefit from the establishment of the species formed.

The metabolite and gene networks can be deciphered through assimilation of the data of metabolomics and transcriptomics [83]. For example, the proteomics and the metabolomics were integrated to establish the response of Arabidopsis to cesium stress [84]. However, in view of the problem of data integration, the collective study of the data from metabolomics and other omics is actually challenging [85].

Though other targets for approaches related to genomics are attainable, to identify metabolites produced in streptomycetes grown in growth media with 0. This would help to decipher cluster of genes during metal stress [86]. Metals could be used as inducers of new metabolites such as antibiotics i. A good approach to metallo-metabolomics should help in element identification in the species or identifies at least some and account clearly for the non-identified ones quantitative speciation blueprint.

In contrast to metallo-proteomics, the de novo recognition of metabolites is performed by using leading spectrometric techniques. Mass spectrometry MS technology and a purification method are a comprehensive approach to metallo-metabolomics [11]. The sensitivity of ICP-MS is autonomous of the metalloid surroundings of the molecule, concomitant compounds, and buffer used for chromatography and the matrix. This is an important attribute which is not possible to measure through electrospray ionization mass spectrometry ESI-MS. Note that ICP-MS cannot monitor the nature of separation per se but it is considered that analytic purity increases with each separation step when clean volatile buffers are used [16].

The metallo-metabolites are highly polar and less hydrophobic which make hydrophilic interaction chromatography HILIC [87], an optimal approach for sample addition by ESI-MS in metallo-metabolomics. The HILIC is a significant technique to investigate seleno-metabolome of yeast [88], and few organic molecules metal complexes Weber et al. The absence of well-depicted metabolome of plants is a great challenge in metabolomics of plants. Approximately distinct metabolites are produced in plants [90], but the exact statistic of metabolites in any individual plant type is still unknown.


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The microbes have better-understood metabolism, even then the total metabolites present in microbes is not deciphered. The metabolome characterization of the plants is essential in order to uncover the gene function. Metals generally exist in the atmosphere but their level is increasing due to industrial revolution via technological advancements. The increase in a number of metals in ecosystem occurs in metropolitan areas, metalliferous mines, major road systems, vehicle emissions, areas characterized by automobile activities etc.

The increased level of metals in the biosphere is the cause of slow environmental poisoning. Thus, it necessitates studies on environmental pollution and biogeochemistry. Further, the knowledge of how living creatures sense, adapt and use metals in dynamic ecosystem or biome is fundamental for the precise view of the metabolism of transition metals [92].

Metallomics and the cell: some definitions and general comments. - Semantic Scholar

Metallomics comprise various types of information from identification of metals qualitative metallomics to finding out their level quantitative metallomics [14]. Metallomics may be important in studies relevant to plant metal tolerance and homeostasis [93], biogeochemical metal cycles [94], plant proteome annotation engaged in toxicity of metals [95]. Metallomics may be supportive to the improvement of applications for optimized strategies in metal contaminated soils, including microbial-assisted phytoremediation of polluted land, reclamation of soil and biomarker recognition for eco-toxicological studies [94].

For phytoremediation studies, phytochelatins build-up in the plants is significant phenomenon due to their role in detoxification of heavy metals [96].

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The study of plant and soil amount of heavy metals in Opuntia ficus predicated a complex interplay of heavy metals in the environment and phytochelatin production [97]. Many advanced approaches such as HPLC-ICP-MS is utilized in phytoremediation studies for the establishment of seleno-compounds in the plant extracts from Brassica juncea, Allium sativum, [98], and Bertholletia excelsa [99].

In Brassica juncea and Sesuvium portulacastrum, complexes with bio-ligands have been investigated after exposure to different amounts of Pb NO3 2.


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  • Studies have revealed that due to the presence of the isoform phytochelatin3 both the plants are crucial in phytoremediation [96]. Moreover, the metalloproteins have a role as environmental stress biomarkers. The metal and metalloids play a significant function in organisms as large biomolecules nucleic acids, polysaccharides, and proteins and organic molecules oxalate, citrate, tartrate, amino acids, oligopeptides can be bound to metals, to generate different chemical species [3].

    The biomolecules binding metals constitute a considerable quantity of molecules engaged in the metabolism of the cell and assist in identification of metal cofactor present in the protein. This helps to find out the function of the protein in cellular pathways []. For example, metallothioneins are metal binding proteins rich in Cys and are utilized as biomarkers for some organisms exposed to metals in the environment.

    Metallothioneins in the organisms bind metals and thus act as a detoxifying mechanism []. Metallothioneins are utilized to find out the effect of heavy metals in marine organisms []. The method of determination of hepatic metallothioneins is confirmed biomarker for determination of biological implication of metal contamination.

    Other metalloproteins have been established as markers such as metal superoxide dismutase in biological creatures in contact with xenobiotics. Metal superoxide dismutase SOD is studied upon drought stress [], in rice and ozone [], action. The probability of deciphering more metalloproteins that can act as biomarkers for pollution is potentially high in fish. The metalloproteins which are being studied as environmental biomarkers in fish are matrix metalloproteinases, iron-binding metalloproteins, selenoproteins, Hg-, Se- and As- containing proteins and superoxide dismutases.

    The research of the biomolecules using metallomic approach simplifies the significance of complex biological matrices.

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    The interpretation of the structure, elucidation of the pathways, and characterization of the metalloproteins are the areas which require further investigation. Metals not only perform an important function in various crucial processes of life but they are also used as magnetic compasses in living organisms. The various animals such as bees, birds, sea turtles etc. With their compasses, some species navigate entire oceans []. Magnetoreception or magnetoception allows the animals which show biomagnetism magnetic field production by organisms to investigate magnetic field so as to perceive directions.

    Magnetoception illustrates the navigational skills of many animal species []. The phenomenon of magnetoception is noticed in bacteria, birds, fungi, insects and many other animals. Such cellular communication roles by metals are a very exciting frontier in biology.

    Magnetotactic bacteria incorporate magnetosomes magnetite or greigite nanocrystals which help bacteria navigate geomagnetic field to avoid the higher oxygen concentrations of surface waters, which are toxic to them []. The Clumbia livia commonly known as homing pigeon provides the best example of magnetoreception.

    Pigeons have magnetic minerals in the beak that remain in contact with the nerve and react to alteration in a magnetic field []. Likewise, based on behavioral evidence of Apis mellifera or honeybee characteristic of magnetoreception has been provided. Free flying honeybees can perceive static intensity fluctuations as weak as 26nT against the magnetic field [].

    Biomagnitites Fe3O4 are present as magnetoreceptor and play an important role to transduce information of magnetic field. Honeybees go through iron biomineralization which causes magnetoreception []. For example, calcium-binding proteins control functions of the cell and the sodium ions influx into cell membrane causes the neurons to respond.

    Calcium controls many significant cell activities starting with new life creation at fertilization to ending with apoptosis []. Likewise, Zinc fingers are metal ion classes in biology that regulate transcription. These pieces of evidence suggest the importance of metal ions in communication biology. Metal complexes are important to carry out biological and biomedical processes. Metal complexes consist of meal atoms surrounded by ligands.