MECHANISM OF ACTION OF ZINC IN ZINCOVIT AND ZINCOFER TABLETS

1. Zincovit Tablets: Zincovit is an advanced formula of high concentration of vitamins,

essential minerals and Zinc. Zinc has been found to be very important for boosting up
immunity. T-cell producing thymus gland depends on regular supply of zinc for its normal
phagocytic functions including maturation of T-cells. (1)

Mechanism of Action of Zinc in Zincovit Tablets: (2, 3)

Zinc is necessary for the activity of some immunity mediators. This has been clearly shown
for thymulin, a nonapeptidic hormone (Glu-Ala-Lys-Ser-Gln-Gly-Gly-Ser-Asn) secreted
by thymic epithelial cells, and requiring the presence of zinc for its biological activity. This
peptide promotes T lymphocyte maturation, cytotoxicity, and IL-2 production. Zinc is
bound to thymulin in a 1:1 stoichiometry via the side chains of asparagine and the hydroxyl
groups of the two serines. Thymulin activity, in vitro and in vivo, in both animals and
humans, is dependent on plasma zinc concentrations so that marginal changes in zinc
intake or availability affect thymulin activity. Thymulin is detectable in the serum of zinc-
deficient patients, but is not active. The binding of zinc to the peptide results in a
conformational change that produces the active form of thymulin. The use of thymulin as
an indicator of zinc deficiency has been suggested and the assay of serum thymulin activity
with or without zinc addition in vitro may be used as a sensitive criterion for diagnosing
mild zinc deficiency in humans. Zinc could also be critical for some cytokine activity. For
instance, it has been demonstrated that the production or the biological activity of
Interleukins (IL-1, IL-2, IL-3, IL-4, IL-6)*, Interferon (IFN-g)** and Tumor necrosis factor
(TNF-a which helps in the regulation of immune cells.) are affected by zinc deficiency. In
addition, and as mentioned above, zinc deficiency in humans affects the cytokine
production of TH1 cells leading to an imbalance between TH1 and TH2 cells.
*Interleukins are a group of cytokines (secreted proteins/signaling molecules) that were
first seen to be expressed by white blood cells (leukocytes). They promote the development
and differentiation of T-lymphocytes, B-cells or plasma cells, and hematopoietic cells. (4)
**Interferons (IFNs) are proteins made and released by host cells in response to the
presence of pathogens such as viruses, bacteria, parasites or tumor cells. They allow for
 communication between cells to trigger the protective defenses of the immune system that
eradicate pathogens or tumors. (5)

Figure 1: Landscape of zinc effect on immune cells (3)

Zinc is an integral part of a thymic hormone molecule, thymulin. Thymulin is required for maturation of T-
cells. Zinc deficiency-induced decrease in thymulin activity is associated with decreased maturation of T-
cells and Th1 production of IL-2 and INF-g. Decreased IL-2 leads to decreased NK- and T cytolytic cell
activities. Macrophages-monocytes produce IL-12 (a zinc-dependent cytokine), which along with INF-g
kills parasites, viruses and bacteria. Th2 cytokines, in general are not affected by zinc deficiency except IL-
10, which may be increased in zinc deficient elderly individuals. Increased IL-10 from Th2 cells further
affects Th1 functions adversely. Thus, in zinc deficiency there is a shift from Th1 to Th2 functions and
cell-mediated immune functions are impaired. Zinc deficiency also leads to stress and activation of
macrophages-monocytes, resulting in increased generation of inflammatory cytokines, IL-1b, IL-6, IL-8
and TNF-a. Solid lines indicate pathways leading to generation of selected cytokines and dotted lines
represent pathways, which lead to inhibition of cytokine generation. NK represent natural-killer cells; Th1
represent activated Th1 type T- cells and secreted cytokines (small triangles); Th2 represents activated Th2
type T-cells and secreted cytokines (small rounds); B-cell represents B-cell lineages and associated
immunoglobulins (triangles).

2. Zincofer Tablets: Zincofer is the first bimetallic Haematinic - Ferrous fumarate with zinc.

Zinc in Zincofer initiates DNA and RNA synthesis and ensures proper fetus formation. (1)
 Mechanism of Zinc in Zincofer Tablets: (6)
Zinc is present in the cell nucleus, nucleolus and chromosomes, and zinc stabilizes the
structure of DNA, RNA and ribosomes. Numerous enzymes associated with DNA and
RNA synthesis are also zinc metalloenzymes, including RNA polymerase (enzyme that
produces RNA) and reverse transcriptases (enzymes that transcribe ss-RNA to ss-DNA) (7).
The zinc in these enzymes is tightly bound and forms a variety of structures that are
functionally important to the enzyme. One common structure is the zinc finger domains in
which the zinc ion forms a loop in the polypeptide chain by creating a bridge between
cysteine and histidine residues. Many proteins containing zinc fingers have been
discovered, with this motif being one of three considered fundamental for eukaryotic
regulatory proteins to bind specific DNA sequences. The relationships among the clinical
effects of zinc deficiency on embyrogenesis, growth and differentiation and regulation of
the nuclear hormone receptor superfamily were recently reviewed. Because these receptors
are regulated by zinc finger domains, limited zinc availability may impair their
responsiveness and thereby explain the reproductive effects of zinc deficiency.
Zinc appears to regulate thymidine kinase mRNA which helps in the formation of DNA by
catalyzing the conversion of deoxythmidine to deoxythymidine monophosphate- through
zinc-dependent protein binding to the promoter region of the gene. The role of zinc appears
to be through regulation of thymidine kinase transcription, and not mRNA stability.
So, in these two ways zinc regulates the cell differentiation and growth by taking part in
DNA and RNA synthesis.

REFERENCES:
1. www.apexlab.com/products
2. M Dardenne, Zinc and immune function. European Journal of Clinical Nutrition (2002) 56,
Suppl 3, S20 – S23. doi:10.1038=sj.ejcn.1601479
3. Ananda S. Prasad, Zinc: role in immunity, oxidative stress and chronic inflammation,
Current Opinion in Clinical Nutrition and Metabolic Care 2009, 12:646–652.
4. http://en.wikipedia.org/wiki/Interleukin
5. http://en.wikipedia.org/wiki/Interferon
6. Ruth S. MacDonald, The Role of Zinc in Growth and Cell Proliferation, J. Nutr. 130:
1500S—1508S, 2000.
7. http://en.wikipedia.org/wiki/Reverse_transcriptase