BIO5SCS - Literature Review: Zinc's Biological and Chemical Roles

This literature review delves into the multifaceted biological and chemical roles of zinc within the human system, emphasizing its significance in various physiological processes. It examines zinc's involvement in crucial functions such as cell division, where zinc oxide nanoparticles' effects on cell ...Read More

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LITERATURE REVIEW
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Table of Contents
INTRODUCTION......................................................................................................................2
LITERATURE REVIEW...........................................................................................................2
Role of Zinc in Cell division..................................................................................................2
Role of zinc in muscle development......................................................................................3
Role of zinc in sustaining immune response..........................................................................5
Role of zinc in carbohydrate metabolism...............................................................................6
Role of zinc in insulin sensitivity and diabetes control..........................................................6
References..................................................................................................................................9

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Biological and chemical role of zinc in human system and recommended for the
function of metallo - enzymes.
INTRODUCTION
Elevation of oxidative stress has been reported to exacerbate human inflammatory
response and cause cellular senescence. Angiotensin II (Zhang et al., 2017) and zinc elevate
reactive oxygen species, causing senescence of the vascular myocytes and this is a zinc-
dependent senescence process. Zinc triggers the NADPH oxidase activities. Zinc is a
structural element in human proteins and plays a very important role in signal transduction
pathways. To regulate cellular homeostasis (Liu et al., 2015) and to prevent the zinc toxicity,
these cytosolic levels of zinc are controlled at very low levels by zinc transporters. Zn
transporters have been reported to reduce the cytosolic zinc and move zinc out of the cells.
Zinc is regarded as the protective mineral for a vascular health and it is due to zinc’s anti-
inflammatory, antioxidant properties.
LITERATURE REVIEW
Role of Zinc in Cell division
Patel et al., (2016) studies the cellular uptake of zinc oxide epidermal cells, during
cell cycle. The nanoparticles of metal oxide include zinc oxide. The study argues that
nanoparticles have reported success for drug delivery to the target tissues and has also shown
efficiency in targeting of gene delivery while treating cancer. As because anti-cancer
therapeutics (Weinberg and Chandel, 2015) fall short of effective differentiation between
normal and cancerous cells (Lekka, 2016) – the research study identifies the need for
developing a novel medicine delivery system that can ‘switch off’ the cancerous cells.. Zinc
oxide nanoparticles can stimulate cancer cell (oncogene) selectivity, induce cell death,

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oxidative stress and the study finds out the interference patterns in cell cycle progression in
carcinogenesis. The study considers these nanoparticles cellular uptake as a crucial phase of
cellular cycle progression. Cytotoxic properties of Zinc oxide nanoparticles and it’s effect in
various cellular cyclic phases are studied by this research. The study concludes by saying
ZnO NPs results cell death, ROS generation and are able to arrest cell cycle in G 2 /M phase
and S phase.
Role of zinc in muscle development
Oshashi et al., (2015) argues to first analyze zinc’s effects on C2C12 myoblasts
differentiation and also found out that it is zinc that promotes proliferation and inhibits
differentiation along with myogenin expression reduction and formation of myotubes.
Activation of satellite cells can cause them to enter cell cycle, causing proliferation of
progenitor myogenic cells followed by differentiate and fusion to form the myofibers. Zinc is
involved with cell growth, DNA synthesis. According to the study – zinc’s role in myogenic
cells was not researched before and hence, it forms the focus of their aim. Furthermore, the
study used C2C12 reserve cell model in myogenic quiescence in order to investigate function
of zinc in activation of the myogenic cells. Reserve cells that incorporates BrdU was found be
increased when zinc was provided in dose dependent way, increasing fusion rates of insulin
and zinc. Extracellular signal-regulated kinase and Akt downstream the insulin signaling
process and are phosphorylated along zinc treatment. The insulin/zinc combination has been
reported to induce ERK cascade activation. The study concludes that zinc enhances
proliferation of myogenic cells and muscle development through a cascade signaling process.

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Fig 1: insulin signaling pathway
Fig 2: Signal transduction

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Role of zinc in sustaining immune response
Paola et al, (2015) did a literature review showing the nutritional importance of Zinc
in immune modulation. The study aims to review the mechanisms involved in regulation of
the Zn related homeostasis along with their effects on immunological responses (Fu &
Blackshear 2017) implying the physiopathology in rheumatoid arthritis. Zinc functions as an
immune-modulator through bioavailability regulated by regulators, regulators. The study
highlights that any disruption in this aforementioned mechanism, Zinc availability is
minimised, altering the survival, the proliferation and the differentiation of cells, tissue
systems and immunological cells. Zinc deficiency is reported by the study, to affect cells that
are involved in both of the innate and the adaptive immunity during proliferation, maturation
levels. The cells include the monocytes, the polymorphonuclear (Herlihy et al., 2016) the
natural killer, the T and the B lymphocyte cells. T cellular functions and population of helper
T cells changes with Zinc status. While the acute Zinc deficiency elicits a decrease in both of
the innate and the adaptive immunity - deficiency level increases the inflammation. During
this chronic deficiency, production of the pro-inflammatory population of cytokines increases
that influences outcome of inflammatory pathologies which includes rheumatoid arthritis as
well.

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Fig 3: T- cell activation pathway
Role of zinc in carbohydrate metabolism
Samir and Zine (2016) aimed to investigate zinc supplementation’s effect on bodily
zinc status, metabolism of carbohydrate and enzymatic activities in alloxan-induced diabetic
rats. A randomized controlled study was done and groups were copper + zinc, diabetes +
copper, copper and diabetes + copper + zinc. Diabetes in the fourth, fifth and sixth groups
was induced by alloxan. The findings of this copper supplementation study showed a
significant fall in the weight gain, tissue zinc, serum zinc and serum protein levels, and levels
of alkaline phosphatase, amylase and lactic dehydrogenase activities. The study concluded
that the changes are related to creatinine, transaminases, uric acid augmentation in both type
of rats without and with diabetes. Zinc supplementation thus shows a marked alteration in
carbohydrate metabolism. The study concludes by showing the positive effects of zinc in both
diabetic, non-diabetic rats.
Role of zinc in insulin sensitivity and diabetes control
Guy et al., (2015) focused on the recent researches which assessed free zinc in the
subcellular compartments and those studies that dissected the function of intracellular located
zinc in control of the glucose homeostasis in vivo and in vitro. The study discusses the
specific effects such as insulin secretion, action of deleting over-expressive genes in beta
cells of pancreatic islet and focuses on zinc’s role in insulin signaling. In vitro analyses
depicted that the insulin lead to increase in the intracellular levels of zinc. While free
concentration of zinc ions in endoplasmic reticulum has been research intricacy - it was
suggested about zinc importer proteins may be involved in a rapid action-mediated epidermal
growth factor, which uses the same signaling pathway like insulin. The studies that are
reviewed by this research stretches from genetics to rat models to devising of new imaging
modalities – provided new insights on the signaling pathways of insulin. The study strongly

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supports the compelling evidence that indicate that these ions of zinc play a vital role in
hormone mediated pathways, modulating its action on target tissues and this study suggests
that the Zn ions can be considered as vital intra-cellular and extra cellular signaling species.
The implications and findings of this research are significant and quite relevant to its aim.
Cruz, Oliviera and Marriero, (2015) performed a bibliographical survey through the
database of Scielo, Pubmed and Lilacs, without any limit on the publication year, considering
that the inclusion criteria: of studies that has evaluated effect of nutritional zinc’s
supplementation on the metabolism and on the oxidative stress markers in diabetes mellitus
Type 2. The scholarly articles was selected on basis of relevance and originality, considering
both of the accuracy and the adequacy of experimental design, physiological type, sample
size and recruited performance measures. Both classic and the recent works are used. The
review found strong evidences for increased plasma and erythrocyte zinc concentrations in
diabetes type 2 patients as compared to control group. This study uses scientific journals of
different ethnicities to validate results and findings. The researchers suggested that the
plasma values should be linked to diagnosis time of the concerned disease that is higher at the
start. The study identified the factor that favors an increase in zinc ion concentration in the
erythrocytes - the oxidative stress induced by the diabetes mellitus type 2 is more due to
erythrocytes that consequently increases the cellular and blood levels antioxidants as a
compensatory protective mechanism.
CONCLUSION
Hence, it can be concluded saying that zinc perform a number of vital physiological,
biochemical processes in the body such as cell division, muscle development, sustaining
immunological responses, carbohydrate Metabolism, insulin sensitivity and in diabetes

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control. The above literature with their merits, limitations and critical evaluation – makes a
good effort in studying each of the functions.

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References
Bonaventura, P., Benedetti, G., Albarède, F. and Miossec, P. Zinc and its role in immunity
and inflammation. Autoimmunity reviews, 14(4), 2015 pp.277-285.
Cruz, K.J.C., de Oliveira, A.R.S. and do Nascimento Marreiro, D. Antioxidant role of zinc in
diabetes mellitus. World journal of diabetes 2015 6(2), p.333.
Derouiche, S. and Kechrid, Z., Zinc supplementation overcomes effects of copper on zinc
status, carbohydrate metabolism and some enzyme activities in diabetic and nondiabetic
rats. Canadian journal of diabetes, 40(4) 2016, pp.342-347.
Fu, M., & Blackshear, P. J. RNA-binding proteins in immune regulation: a focus on CCCH
zinc finger proteins. Nature Reviews Immunology 2017, 17(2), 130.
Herlihy, S.E., Ramachandran, I., Condamine, T., Lin, C., Garfall, A., Vogl, D., Gabrilovich,
D. and Nefedova, Y. Ly6G+ neutrophils and polymorphonuclear-myeloid derived suppressor
cells promote the survival of tumor cells. 2016
Liu, Y., Batchuluun, B., Ho, L., Zhu, D., Prentice, K.J., Bhattacharjee, A., Zhang, M.,
Pourasgari, F., Hardy, A.B., Taylor, K.M. and Gaisano, H. Characterization of Zinc Influx
Transporters (ZIPs) in Pancreatic β Cells Roles in Regulating Cytosolic Zinc Homeostasis
and Insulin Secretion. Journal of Biological Chemistry, 290(30), 2015, pp.18757-18769.
Ohashi, K., Nagata, Y., Wada, E., Zammit, P.S., Shiozuka, M. and Matsuda, R. Zinc
promotes proliferation and activation of myogenic cells via the PI3K/Akt and ERK signaling
cascade. Experimental cell research, 2015, 333(2), pp.228-237.
Patel, P.; Kansara, K.; Senapati, V.; Shanker, R.; Dhawan, A.; Kumar, A. Cell Cycle
Dependent Cellular Uptake Of Zinc Oxide Nanoparticles In Human Epidermal
Cells. Mutagenesis, 2016, 31, 481-490.

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Rutter, G.A., Chabosseau, P., Bellomo, E.A., Maret, W., Mitchell, R.K., Hodson, D.J.,
Solomou, A. and Hu, M., Intracellular zinc in insulin secretion and action: a determinant of
diabetes risk? Proceedings of the Nutrition Society, 2016, 75(1), pp.61-72.
Suzuki, K., Sako, K., Akiyama, K., Isoda, M., Senoo, C., Nakajo, N., & Sagata, N.
Identification of non-Ser/Thr-Pro consensus motifs for Cdk1 and their roles in mitotic
regulation of C2H2 zinc finger proteins and Ect2. Scientific reports, 2015, 5, 7929.
Weinberg, S.E. and Chandel, N.S Targeting mitochondria metabolism for cancer therapy.
Natu Lekka, M. Discrimination between normal and cancerous cells using AFM.
Bionanoscience, 6(1), 65-80.re chemical biology, 2016, 11(1), p.9.
Zhang, H., Han, G.W., Batyuk, A., Ishchenko, A., White, K.L., Patel, N., Sadybekov, A.,
Zamlynny, B., Rudd, M.T., Hollenstein, K. and Tolstikova, A. Structural basis for selectivity
and diversity in angiotensin II receptors. Nature, 544(7650), 2017, p.327.]